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Volume 27,Issue 6,2020 Table of Contents
2020, 27(6):593-601.
DOI: 10.3872/j.issn.1007-385X.2020.06.001
Abstract:
Cancer-associated fibroblasts (CAFs) are one of the predominant stromal cells that constitute the tumor microenvironment,and play an essential role in tumor growth, metastasis, chemoresistance and tumor immunity. Autophagy is a cellular process through which cells degrade products in the metabolic process and reuse them to respond to environmental stress. Autophagy is important for tumor initiation, progression and response to therapy, as it connects cellular homeostasis with the extracellular environment that affects immunity and metabolism. This review, by introducing the role of autophagy in CAFs and its regulatory mechanism, summarizes the research progress on studies of autophagy in CAFs and tumor metabolism, progression, metastasis and resistance to therapy.
Cancer-associated fibroblasts (CAFs) are one of the predominant stromal cells that constitute the tumor microenvironment,and play an essential role in tumor growth, metastasis, chemoresistance and tumor immunity. Autophagy is a cellular process through which cells degrade products in the metabolic process and reuse them to respond to environmental stress. Autophagy is important for tumor initiation, progression and response to therapy, as it connects cellular homeostasis with the extracellular environment that affects immunity and metabolism. This review, by introducing the role of autophagy in CAFs and its regulatory mechanism, summarizes the research progress on studies of autophagy in CAFs and tumor metabolism, progression, metastasis and resistance to therapy.
2020, 27(6):602-608.
DOI: 10.3872/j.issn.1007-385X.2020.06.002
Abstract:
Objective: This study aimed at investigating the epigenetic regulation mechanism of abnormally low expression of SHP-1 gene in esophageal squamous cell carcinoma (ESCC). Methods: A total of 71 cases of ESCC tissues and corresponding para-cancer tissues(2 cm from the edge of the cancer) resected during surgery at the Department of thoracic surgery of Hebei Province, the Fourth Hospital of Hebei Medical University from 2008 to 2011 were collected for this study. The expression level of SHP-1 mRNA and protein was detected in esophageal cancer cell lines (Eca109, Kyse170, Yes-2) before and after 5-Aza-dC or TSA treatment by RT-qPCR and Western blotting methods respectively. The methylation status of CpG sites in promoter region of SHP-1 was analyzed by bisulfite genome sequencing (BGS) in three esophageal cancer cell lines before and after 5-Aza-dC treatment. The methylation status of SHP-1 was studied by methylation-specific polymerase chain reaction (MSP) method in esophageal cancer cell lines, ESCC tissues and para-cancer tissues. The association between the SHP-1 promoter methylation status and clinic pathological parameters were analyzed in ESCC patients. Dual-luciferase reporter assay systems method was applied to detect the impacts of methylation status of CpG island in SHP-1 promoter region on gene transcription activity. For prognostic analysis of SHP-1 methylation, survival curves were constructed using the Kaplan-Meier method and the log-rank. Results: After treated with 5-Aza-dC, the expression level of SHP-1 mRNA and protein was significantly up-regulated in Eca109, Kyse170 and Yes-2 cells, meanwhile the methylation status of SHP-1 was decreased (P<0.05). The expression level of SHP-1 had no obviously change after treated with trichostatin A(TSA). The methylation frequency of promoter in ESCC tumor tissues was significantly higher than that in corresponding para-cancer tissues (P<0.05). When stratified for clinic pathologic characteristics, methylation frequency of SHP-1 was associated with TNM stage, pathological differentiation,and LN metastasis (P<0.05). The mRNA expression level of SHP-1 in the ESCC tissues with SHP-1 methylation was significantly decreased compared to the ESCC tissues with unmethylation of SHP-1 (P<0.05). It was associated with methylation of promoter (P<0.05). The activity of fluorescein reporter vector in methylase treatment group was significantly lower than that in untreated group (P<0.05), indicating that SHP-1expression can be silenced by methylation of SHP-1 promoter. The result of Kaplan-Meier shown that SHP-1 promoter methylation was correlated with ESCC patients’poor survival. Conclusion: The transcriptional activity of SHP-1 can be inhibited with hypermethylated SHP-1 promoter region. The hypermethylated SHP-1 promoter induced the silencing of SHP-1.Therefore, SHP-1 gene may serve as one of prognostic methylation biomarkers for ESCC patients.
Objective: This study aimed at investigating the epigenetic regulation mechanism of abnormally low expression of SHP-1 gene in esophageal squamous cell carcinoma (ESCC). Methods: A total of 71 cases of ESCC tissues and corresponding para-cancer tissues(2 cm from the edge of the cancer) resected during surgery at the Department of thoracic surgery of Hebei Province, the Fourth Hospital of Hebei Medical University from 2008 to 2011 were collected for this study. The expression level of SHP-1 mRNA and protein was detected in esophageal cancer cell lines (Eca109, Kyse170, Yes-2) before and after 5-Aza-dC or TSA treatment by RT-qPCR and Western blotting methods respectively. The methylation status of CpG sites in promoter region of SHP-1 was analyzed by bisulfite genome sequencing (BGS) in three esophageal cancer cell lines before and after 5-Aza-dC treatment. The methylation status of SHP-1 was studied by methylation-specific polymerase chain reaction (MSP) method in esophageal cancer cell lines, ESCC tissues and para-cancer tissues. The association between the SHP-1 promoter methylation status and clinic pathological parameters were analyzed in ESCC patients. Dual-luciferase reporter assay systems method was applied to detect the impacts of methylation status of CpG island in SHP-1 promoter region on gene transcription activity. For prognostic analysis of SHP-1 methylation, survival curves were constructed using the Kaplan-Meier method and the log-rank. Results: After treated with 5-Aza-dC, the expression level of SHP-1 mRNA and protein was significantly up-regulated in Eca109, Kyse170 and Yes-2 cells, meanwhile the methylation status of SHP-1 was decreased (P<0.05). The expression level of SHP-1 had no obviously change after treated with trichostatin A(TSA). The methylation frequency of promoter in ESCC tumor tissues was significantly higher than that in corresponding para-cancer tissues (P<0.05). When stratified for clinic pathologic characteristics, methylation frequency of SHP-1 was associated with TNM stage, pathological differentiation,and LN metastasis (P<0.05). The mRNA expression level of SHP-1 in the ESCC tissues with SHP-1 methylation was significantly decreased compared to the ESCC tissues with unmethylation of SHP-1 (P<0.05). It was associated with methylation of promoter (P<0.05). The activity of fluorescein reporter vector in methylase treatment group was significantly lower than that in untreated group (P<0.05), indicating that SHP-1expression can be silenced by methylation of SHP-1 promoter. The result of Kaplan-Meier shown that SHP-1 promoter methylation was correlated with ESCC patients’poor survival. Conclusion: The transcriptional activity of SHP-1 can be inhibited with hypermethylated SHP-1 promoter region. The hypermethylated SHP-1 promoter induced the silencing of SHP-1.Therefore, SHP-1 gene may serve as one of prognostic methylation biomarkers for ESCC patients.
2020, 27(6):609-614.
DOI: 10.3872/j.issn.1007-385X.2020.06.003
Abstract:
Objective: To investigate the anti-tumor effect and mechanism of new LL-37 hybrid peptide on breast cancer MCF-7 cells.Methods: Human antimicrobial peptide LL-37 and human neutrophil peptide 1(HNP-1) were screened by using of Antimicrobial Peptides Database (http:// aps.unmc.edu/AP/main.php). The new LL-37 hybrid peptide was synthesized by integrating the active fragments,which were selected by bioinformatics analysis. The breast cancer MCF-7 cells and human normal breast MCF10A cells were treated with the new LL-37 hybrid peptides (0~70 μmol/L). Cell viability was monitored by CCK-8 assay and the affinity of the new LL-37 hybrid peptide with MCF-7 cells was observed using confocal laser scanning microscope (CLSM). The effects of LL-37 and caspase inhibitor on apoptosis and cell cycle of MCF-7 cells were measured by FCM (flow cytometry). Results: The new LL-37 hybrid peptide, as an amphiphilic cationic polypeptide, could selectively inhibit the proliferation of breast cancer MCF-7 cells (P<0.05) with an IC50 of 58.34 μmol/L, but exerted no significant effect on normal breast MCF10A cells. LL-37 peptide had high affinity with MCF-7 cells, which could cause S-stage stagnation and significantly increased early apoptosis (P<0.01); however, the cell cycle block and apoptosis were significantly attenuated after the treatment of caspase inhibitor (P<0.01). Conclusion: The new LL-37 hybrid peptide has anti-tumor activity on breast cancer MCF-7 cells, and could induce MCF-7 cells apoptosis possibly by arresting cell cycle via the caspase-dependent signaling pathway.
Objective: To investigate the anti-tumor effect and mechanism of new LL-37 hybrid peptide on breast cancer MCF-7 cells.Methods: Human antimicrobial peptide LL-37 and human neutrophil peptide 1(HNP-1) were screened by using of Antimicrobial Peptides Database (http:// aps.unmc.edu/AP/main.php). The new LL-37 hybrid peptide was synthesized by integrating the active fragments,which were selected by bioinformatics analysis. The breast cancer MCF-7 cells and human normal breast MCF10A cells were treated with the new LL-37 hybrid peptides (0~70 μmol/L). Cell viability was monitored by CCK-8 assay and the affinity of the new LL-37 hybrid peptide with MCF-7 cells was observed using confocal laser scanning microscope (CLSM). The effects of LL-37 and caspase inhibitor on apoptosis and cell cycle of MCF-7 cells were measured by FCM (flow cytometry). Results: The new LL-37 hybrid peptide, as an amphiphilic cationic polypeptide, could selectively inhibit the proliferation of breast cancer MCF-7 cells (P<0.05) with an IC50 of 58.34 μmol/L, but exerted no significant effect on normal breast MCF10A cells. LL-37 peptide had high affinity with MCF-7 cells, which could cause S-stage stagnation and significantly increased early apoptosis (P<0.01); however, the cell cycle block and apoptosis were significantly attenuated after the treatment of caspase inhibitor (P<0.01). Conclusion: The new LL-37 hybrid peptide has anti-tumor activity on breast cancer MCF-7 cells, and could induce MCF-7 cells apoptosis possibly by arresting cell cycle via the caspase-dependent signaling pathway.
2020, 27(6):615-621.
DOI: 10.3872/j.issn.1007-385X.2020.06.004
Abstract:
Objective: To investigate the effect of Beclin1 knockdown on cisplatin resistance in ovarian cancer A2780 cells and its related mechanisms. Methods: The mRNA and protein expressions of Beclin1 in A2780 cells and drug resistant A2780/DDP cells were determined by qPCR and Western blotting. After transfection with Beclin1 siRNA, the sensitivity of A2780/DDP cells to cisplatin was detected by MTT assay; Cell clone formation and apoptosis were detected by the Colony formation assay and Flow cytometry assay, respectively; cell autophagy was monitored by monodansylcadaverin (MDC) staining. Furthermore, the protein levels of cell autophagy related proteins, lysosomal associated membrane protein Lamp-2 and Cathepsin B were detected by Western blotting.Results: The mRNA and protein expression levels of Beclin1 in cisplatin-resistant A2780/DDP cells were significantly higher than those in A2780 cells (all P<0.05). The expression of Beclin1 was significantly increased in A2780 cells after treated with cisplatin (P<0.05). Beclin1 knockdown promoted cisplatin induced apoptosis of A2780/DDP cells (P<0.05), inhibited autophagy and cell colony formation (all P<0.05), and increased cell sensitivity to cisplatin (P<0.05). Meanwhile, Western blotting showed that Beclin1 knockdown increased the protein levels of cleaved-caspase 3 and Cathepsin B in A2780/DDP cells, while down-regulated the protein expressions of Atg3, Atg7, LC3Ⅱ/Ⅰ and Lamp-2 (all P<0.05). Conclusion: Beclin1 knockdown can improve the sensitivity of A2780/DDP cells to cisplatin, and the mechanism may be related to the inhibition of protective autophagy of cells by regulating the expressions of autophagy related proteins, and the regulation of lysosomes, thus further promoting cisplatin-induced apoptosis of drug-resistant cells.
Objective: To investigate the effect of Beclin1 knockdown on cisplatin resistance in ovarian cancer A2780 cells and its related mechanisms. Methods: The mRNA and protein expressions of Beclin1 in A2780 cells and drug resistant A2780/DDP cells were determined by qPCR and Western blotting. After transfection with Beclin1 siRNA, the sensitivity of A2780/DDP cells to cisplatin was detected by MTT assay; Cell clone formation and apoptosis were detected by the Colony formation assay and Flow cytometry assay, respectively; cell autophagy was monitored by monodansylcadaverin (MDC) staining. Furthermore, the protein levels of cell autophagy related proteins, lysosomal associated membrane protein Lamp-2 and Cathepsin B were detected by Western blotting.Results: The mRNA and protein expression levels of Beclin1 in cisplatin-resistant A2780/DDP cells were significantly higher than those in A2780 cells (all P<0.05). The expression of Beclin1 was significantly increased in A2780 cells after treated with cisplatin (P<0.05). Beclin1 knockdown promoted cisplatin induced apoptosis of A2780/DDP cells (P<0.05), inhibited autophagy and cell colony formation (all P<0.05), and increased cell sensitivity to cisplatin (P<0.05). Meanwhile, Western blotting showed that Beclin1 knockdown increased the protein levels of cleaved-caspase 3 and Cathepsin B in A2780/DDP cells, while down-regulated the protein expressions of Atg3, Atg7, LC3Ⅱ/Ⅰ and Lamp-2 (all P<0.05). Conclusion: Beclin1 knockdown can improve the sensitivity of A2780/DDP cells to cisplatin, and the mechanism may be related to the inhibition of protective autophagy of cells by regulating the expressions of autophagy related proteins, and the regulation of lysosomes, thus further promoting cisplatin-induced apoptosis of drug-resistant cells.
2020, 27(6):622-628.
DOI: 10.3872/j.issn.1007-385X.2020.06.005
Abstract:
Objective: To investigate the role of miR-125a-5p in inducing the gefitinib (Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). And the influences of Gef onA549/GR cells were enhanced by knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1,miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05).Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation,migration and inhibition of apoptosis of non-small cell lung cancer cells by targeting APAF1.
Objective: To investigate the role of miR-125a-5p in inducing the gefitinib (Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). And the influences of Gef onA549/GR cells were enhanced by knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1,miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05).Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation,migration and inhibition of apoptosis of non-small cell lung cancer cells by targeting APAF1.
WU Meiqin
,
WANG Yong
,
ZHU Hongfei
,
SONG Xiaojie
,
LI Yuxia
,
LIU Zhihui
,
ZHAO Shuyan
,
YUAN Jing
,
GONG Jingjing
,
LIANG Xing
,
CHEN Dandan
,
NING Xiangcheng
2020, 27(6):629-633.
DOI: 10.3872/j.issn.1007-385X.2020.06.006
Abstract:
Objective: To investigate the effect of HMGB1 gene on the growth of human epithelial ovarian cancer xenografts in nude mice, and to lay a foundation for finding new targets for the treatment of ovarian cancer. Methods: Human epithelial ovarian cancer SKOV3 cells in logarithmic growth phase were selected to establish a human epithelial ovarian cancer xenograft model in nude mice.Nude mice with successful model establishment were randomly divided into control group and HMGB1-siRNA group. On the 7th, 9th,11th, 14th, and 16th days after cell inoculation, the same amount of saline and HMGB1-siRNA were respectively injected into two groups of mice under the armpit. After 3 weeks, the nude mice were sacrificed by cervical dislocation, the tumor tissues were separated,and the volume of the tumor was measured. The apoptosis of transplanted tumor cells was detected by Tunnel staining. The expressions of HMGB1, STAT3 and p-STAT3 were detected by Western blotting. The expression of vascular endothelial growth factor A (VEGF-A)and microvascularization were detected by immunohistochemistry. Results: Compared with the control group, the growth of tumor volume slowed down in HMGB1 siRNA group, and on the 21st day, the tumor volume of HMGB1-siRNA group was significantly smaller than that of the control group (P<0.05). HMGB1-siRNA successfully knocked down the expression of HMGB1 mRNA in transplanted tumor tissue. The apoptosis rate of tissue cells in HMGB1-siRNA group was significantly increased ([34±8]% vs [6±2]%, P=0.04), and the expressions of HMGB1 and p-STAT3 were significantly reduced (P<0.05). The expression of VEGF-A and the number of microvessels were significantly lower than those of the control group (both P<0.05). Conclusion: Knockdown of HMGB1 gene reduces the expression of VEGF-A and microvessel formation possibly by inhibiting the HMGB1/STAT3 signaling pathway, thereby promoting the apoptosis of tumor tissues and slowing the growth of xenografts.
Objective: To investigate the effect of HMGB1 gene on the growth of human epithelial ovarian cancer xenografts in nude mice, and to lay a foundation for finding new targets for the treatment of ovarian cancer. Methods: Human epithelial ovarian cancer SKOV3 cells in logarithmic growth phase were selected to establish a human epithelial ovarian cancer xenograft model in nude mice.Nude mice with successful model establishment were randomly divided into control group and HMGB1-siRNA group. On the 7th, 9th,11th, 14th, and 16th days after cell inoculation, the same amount of saline and HMGB1-siRNA were respectively injected into two groups of mice under the armpit. After 3 weeks, the nude mice were sacrificed by cervical dislocation, the tumor tissues were separated,and the volume of the tumor was measured. The apoptosis of transplanted tumor cells was detected by Tunnel staining. The expressions of HMGB1, STAT3 and p-STAT3 were detected by Western blotting. The expression of vascular endothelial growth factor A (VEGF-A)and microvascularization were detected by immunohistochemistry. Results: Compared with the control group, the growth of tumor volume slowed down in HMGB1 siRNA group, and on the 21st day, the tumor volume of HMGB1-siRNA group was significantly smaller than that of the control group (P<0.05). HMGB1-siRNA successfully knocked down the expression of HMGB1 mRNA in transplanted tumor tissue. The apoptosis rate of tissue cells in HMGB1-siRNA group was significantly increased ([34±8]% vs [6±2]%, P=0.04), and the expressions of HMGB1 and p-STAT3 were significantly reduced (P<0.05). The expression of VEGF-A and the number of microvessels were significantly lower than those of the control group (both P<0.05). Conclusion: Knockdown of HMGB1 gene reduces the expression of VEGF-A and microvessel formation possibly by inhibiting the HMGB1/STAT3 signaling pathway, thereby promoting the apoptosis of tumor tissues and slowing the growth of xenografts.
2020, 27(6):634-639.
DOI: 10.3872/j.issn.1007-385X.2020.06.007
Abstract:
Objective: To explore the mechanism of miR-145-5p on malignant biological behaviors, such as pro-liferation, invasion,migration and epithelial-mesenchymal transition (EMT), of esophageal squamous cell carcinoma (ESCC) TE-10 cells. Methods: The expression of miR-145-5p in ESCC cell lines and normal cells was detected by PCR. Dual luciferase reporter gene assay was used to detect the targeted regulation between miR-145-5p and insulin-like growth factor 1 receptor (IGF1R). The expres-sions of IGF1R protein and EMT related proteins were detected by Western blotting. Transwell assay and CCK-8 assay were carried out to detect the effects of miR-145-5p/IGF1R axis on the proliferation, migration and invasion of TE-10 cells. Results: miR-145-5p was down-regulated in ESCC cell lines with the lowest expression in TE-10 cells (P<0.01 or P<0.05). Over-expression of miR-145-5p significantly inhibited proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Dual luciferase reporter gene assay con-firmed that miR-145-5p targetedly down-regulated IGF1R expression (P<0.01). The restora-tion experiments further confirmed that simultaneous over-expression of miR-145-5p and IGF1R significantly attenuated the promotion effect of IGF1R on proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Conclusions: Over-expression of miR-145-5p inhibits proliferation, invasion, migration and EMT of ESCC TE-10 cells by down-regulating IGF1R.
Objective: To explore the mechanism of miR-145-5p on malignant biological behaviors, such as pro-liferation, invasion,migration and epithelial-mesenchymal transition (EMT), of esophageal squamous cell carcinoma (ESCC) TE-10 cells. Methods: The expression of miR-145-5p in ESCC cell lines and normal cells was detected by PCR. Dual luciferase reporter gene assay was used to detect the targeted regulation between miR-145-5p and insulin-like growth factor 1 receptor (IGF1R). The expres-sions of IGF1R protein and EMT related proteins were detected by Western blotting. Transwell assay and CCK-8 assay were carried out to detect the effects of miR-145-5p/IGF1R axis on the proliferation, migration and invasion of TE-10 cells. Results: miR-145-5p was down-regulated in ESCC cell lines with the lowest expression in TE-10 cells (P<0.01 or P<0.05). Over-expression of miR-145-5p significantly inhibited proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Dual luciferase reporter gene assay con-firmed that miR-145-5p targetedly down-regulated IGF1R expression (P<0.01). The restora-tion experiments further confirmed that simultaneous over-expression of miR-145-5p and IGF1R significantly attenuated the promotion effect of IGF1R on proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Conclusions: Over-expression of miR-145-5p inhibits proliferation, invasion, migration and EMT of ESCC TE-10 cells by down-regulating IGF1R.
2020, 27(6):640-645.
DOI: 10.3872/j.issn.1007-385X.2020.06.008
Abstract:
Objective: To investigate the effect of long non-coding RNA (lncRNA)-CCAT2 on the proliferation and cell cycle of cervical cancer cells. Methods: The expression of CCAT2 in 3 cervical cancer cell lines (HeLa, C-33A, and CaSki) was detected by qPCR and the cell line with the highest expression level was selected for subsequent experiments. CCAT2 overexpression and interference vectors were designed and synthesized. After transfection, qPCR was performed to detect the transfection efficiency. The cells were divided into 5 groups: control, sh-EV (empty vector), overExp-EV, sh-CCAT2, and overExp-CCAT2. MTT assay was performed to evaluate cell viability. Flow cytometry was performed to measure cell cycle. WB was performed to detect the expressions of Ki67, cyclin D1, and cyclin dependent kinase 4 (CDK4). Results: Among HeLa, C-33A, and CaSki cells, the highest expression of CCAT2 was found in CaSki cells. CCAT2 overexpression and interference vectors were successfully transfected into the CaSki cells.Compared with the control group, the cells viability and proliferation in the sh-CCAT2 group was significantly decreased (all P<0.01),the proportion of cells in the G1 phase was significantly increased (P<0.01), and the expression levels of Ki67, cyclin D1, and CDK4 were significantly decreased (all P<0.01). However, in the overExp-CCAT2 group, the cell proliferation was enhanced and the expression levels of Ki67, cyclin D1, and CDK4 were significantly increased (all P<0.01). Conclusion: CCAT2 affects proliferation and cell cycle of cervical cancer cells by regulating the expressions of their associated proteins.
Objective: To investigate the effect of long non-coding RNA (lncRNA)-CCAT2 on the proliferation and cell cycle of cervical cancer cells. Methods: The expression of CCAT2 in 3 cervical cancer cell lines (HeLa, C-33A, and CaSki) was detected by qPCR and the cell line with the highest expression level was selected for subsequent experiments. CCAT2 overexpression and interference vectors were designed and synthesized. After transfection, qPCR was performed to detect the transfection efficiency. The cells were divided into 5 groups: control, sh-EV (empty vector), overExp-EV, sh-CCAT2, and overExp-CCAT2. MTT assay was performed to evaluate cell viability. Flow cytometry was performed to measure cell cycle. WB was performed to detect the expressions of Ki67, cyclin D1, and cyclin dependent kinase 4 (CDK4). Results: Among HeLa, C-33A, and CaSki cells, the highest expression of CCAT2 was found in CaSki cells. CCAT2 overexpression and interference vectors were successfully transfected into the CaSki cells.Compared with the control group, the cells viability and proliferation in the sh-CCAT2 group was significantly decreased (all P<0.01),the proportion of cells in the G1 phase was significantly increased (P<0.01), and the expression levels of Ki67, cyclin D1, and CDK4 were significantly decreased (all P<0.01). However, in the overExp-CCAT2 group, the cell proliferation was enhanced and the expression levels of Ki67, cyclin D1, and CDK4 were significantly increased (all P<0.01). Conclusion: CCAT2 affects proliferation and cell cycle of cervical cancer cells by regulating the expressions of their associated proteins.
9 Effect of lncRNA PCGEM1 on malignant biological behavior of lung cancer A549 cells and its mechanism
2020, 27(6):646-652.
DOI: 10.3872/j.issn.1007-385X.2020.06.009
Abstract:
Objective ：To investigate the long-chain noncoding RNA (Lnc RNA) PCGEM1 regulating the lung cancer (LC)cell invasion and metastasis through the TGF-β/Smad signaling pathways. Methods：From March 2016 to May 2018, total 62 cases of LC patients receiving surgical treatment in our hospital were collected, including cancer tissues and normal tissues more than 2 cm away from the cancer tissues. qRT-PCR was used to detect the expression of lncRNA PCGEM1 and miR-148a in LC, corresponding para-cancer tissues and different LC cell strains. LncRNA PCGEM1 silenced cell line A549-siPCGEM1 and negative control A549-NC were constructed, and A549 was used as blank control. MTT and plate cloning assay were used to detect the effect of PCGEM1 on the proliferation of A549 cells. Transwell and scratch assay were used to detect the effect of PCGEM1 on the invasion and migration of A549 cells. The bioinformatics website StarBase was used to predict the complementary binding miRNA of PCGEM1. Furthermore, according to the website Targetscan, the genes that the corresponding miRNAs could target and bind were predicted. Results：qRT-PCR results showed that the expression of PCGEM1 in LC tissues and lung cancer cell lines was higher than that in normal tissues, and the expression level of miR-148a was lower than that in normal tissues (all P<0.05). The expression level of PCGEM1 in A549 cells was the highest, and the difference was statistically significant compared with other cell lines (P<0.05). After successful construction of PCGEM1 silenced cells, compared with the blank control group and A549-NC group, the cell OD492nm value of A549-siPCGEM1 group was significantly decreased, the number of cell clones and the number of matrigel matrix gels was significantly reduced, the cell migration rate was significantly reduced, the differences were statistically significant (P<0.05). According to the prediction results of StarBase website, PCGEM1 could be complementary to miR-148a, and the prediction analysis on microRNA.org website shows that miR-148a had a targeted binding site with TGF-β2. qRT-PCR and Western blotting results showed that the expression of miR-148a was significantly increased in the A549-siPCGEM1 group compared with the blank control group and A549-NC group, and the expression of TGF-β2 and p-Smad 2 was significantly decreased (P<0.05), while the expression of the above indicators in the blank control group and A549-NC group was not statistically significant (P>0.05). Conclusion：Lnc RNA PCGEM1 is highly expressed in lung cancer.High expression of PCGEM1 may enhance the TGF-β2/Smad2 signaling pathway by downregulation of miR-148a, thus promoting the development of LC and the malignant biological behavior.
Objective ：To investigate the long-chain noncoding RNA (Lnc RNA) PCGEM1 regulating the lung cancer (LC)cell invasion and metastasis through the TGF-β/Smad signaling pathways. Methods：From March 2016 to May 2018, total 62 cases of LC patients receiving surgical treatment in our hospital were collected, including cancer tissues and normal tissues more than 2 cm away from the cancer tissues. qRT-PCR was used to detect the expression of lncRNA PCGEM1 and miR-148a in LC, corresponding para-cancer tissues and different LC cell strains. LncRNA PCGEM1 silenced cell line A549-siPCGEM1 and negative control A549-NC were constructed, and A549 was used as blank control. MTT and plate cloning assay were used to detect the effect of PCGEM1 on the proliferation of A549 cells. Transwell and scratch assay were used to detect the effect of PCGEM1 on the invasion and migration of A549 cells. The bioinformatics website StarBase was used to predict the complementary binding miRNA of PCGEM1. Furthermore, according to the website Targetscan, the genes that the corresponding miRNAs could target and bind were predicted. Results：qRT-PCR results showed that the expression of PCGEM1 in LC tissues and lung cancer cell lines was higher than that in normal tissues, and the expression level of miR-148a was lower than that in normal tissues (all P<0.05). The expression level of PCGEM1 in A549 cells was the highest, and the difference was statistically significant compared with other cell lines (P<0.05). After successful construction of PCGEM1 silenced cells, compared with the blank control group and A549-NC group, the cell OD492nm value of A549-siPCGEM1 group was significantly decreased, the number of cell clones and the number of matrigel matrix gels was significantly reduced, the cell migration rate was significantly reduced, the differences were statistically significant (P<0.05). According to the prediction results of StarBase website, PCGEM1 could be complementary to miR-148a, and the prediction analysis on microRNA.org website shows that miR-148a had a targeted binding site with TGF-β2. qRT-PCR and Western blotting results showed that the expression of miR-148a was significantly increased in the A549-siPCGEM1 group compared with the blank control group and A549-NC group, and the expression of TGF-β2 and p-Smad 2 was significantly decreased (P<0.05), while the expression of the above indicators in the blank control group and A549-NC group was not statistically significant (P>0.05). Conclusion：Lnc RNA PCGEM1 is highly expressed in lung cancer.High expression of PCGEM1 may enhance the TGF-β2/Smad2 signaling pathway by downregulation of miR-148a, thus promoting the development of LC and the malignant biological behavior.
2020, 27(6):653-657.
DOI: 10.3872/j.issn.1007-385X.2020.06.010
Abstract:
Objective：To study the expression of long non-coding RNA (lncRNA) titin antisense RNA 1 (TTN-AS1) in lung adenocarcinoma (LUAD) tissues, and explore its relationship with clinicopathologic characteristics and prognosis of LUAD patients. Methods:The TTN-AS1 expression in LUAD data set was analyzed using TCGA database. 52 pairs of tumor tissues and matched para-carcinoma tissues from LUAD patients, who underwent surgical resection and were later pathologically conformed in Fourth Hospital of Hebei Medical University between Jan. 2014 and Jan. 2015, were used in this study. qPCR was performed to detect TTN-AS1 expression in the specimens. Then, the correlations between TTN-AS1 expression and clinicopathologic characteristics were analyzed. Survival analysis was used to determine the significance of TTN-AS1 expression for predicting the prognosis of LUAD patients. Results: TCGA database analysis and qPCR results showed that TTN-AS1 expression in LUAD tissues was significantly higher than that in normal lung and para-carcinoma tissues (both P<0.01). TTN-AS1 expression in LUAD tissues was significantly correlated with the TNM stage and lymph node metastasis (P<0.05), but not correlated with gender, age, tumor invasion range (P>0.05). Kaplan-Meier univariate analysis result demonstrated that the patients with high TTN-AS1 expression had shorter post-operative disease-free survival (DFS) and overall survival (OS) than those patients with low TTN-AS1 expression (all P<0.01). Cox proportional hazard regression model result demonstrated that wider tumor invasion range, positive lymph node metastasis and high TTN-AS1 expression were significantly correlated with shorter postoperative DFS and OS (P<0.05). Conclusion: TTN-AS1 was highly expressed in LUAD tissues, and closely correlated with TNM stage and lymph node metastasis of LUAD patients (all P<0.05). High expression of TTN-AS1 is significantly correlated with shorter DFS and OS, indicating that TTN-AS1 may be a biomarker for predicting poor prognosis of LUAD patients.
Objective：To study the expression of long non-coding RNA (lncRNA) titin antisense RNA 1 (TTN-AS1) in lung adenocarcinoma (LUAD) tissues, and explore its relationship with clinicopathologic characteristics and prognosis of LUAD patients. Methods:The TTN-AS1 expression in LUAD data set was analyzed using TCGA database. 52 pairs of tumor tissues and matched para-carcinoma tissues from LUAD patients, who underwent surgical resection and were later pathologically conformed in Fourth Hospital of Hebei Medical University between Jan. 2014 and Jan. 2015, were used in this study. qPCR was performed to detect TTN-AS1 expression in the specimens. Then, the correlations between TTN-AS1 expression and clinicopathologic characteristics were analyzed. Survival analysis was used to determine the significance of TTN-AS1 expression for predicting the prognosis of LUAD patients. Results: TCGA database analysis and qPCR results showed that TTN-AS1 expression in LUAD tissues was significantly higher than that in normal lung and para-carcinoma tissues (both P<0.01). TTN-AS1 expression in LUAD tissues was significantly correlated with the TNM stage and lymph node metastasis (P<0.05), but not correlated with gender, age, tumor invasion range (P>0.05). Kaplan-Meier univariate analysis result demonstrated that the patients with high TTN-AS1 expression had shorter post-operative disease-free survival (DFS) and overall survival (OS) than those patients with low TTN-AS1 expression (all P<0.01). Cox proportional hazard regression model result demonstrated that wider tumor invasion range, positive lymph node metastasis and high TTN-AS1 expression were significantly correlated with shorter postoperative DFS and OS (P<0.05). Conclusion: TTN-AS1 was highly expressed in LUAD tissues, and closely correlated with TNM stage and lymph node metastasis of LUAD patients (all P<0.05). High expression of TTN-AS1 is significantly correlated with shorter DFS and OS, indicating that TTN-AS1 may be a biomarker for predicting poor prognosis of LUAD patients.
2020, 27(6):658-663.
DOI: 10.3872/j.issn.1007-385X.2020.06.011
Abstract:
Objective: To observe the short-term efficacy and safety of Apatinib combined with radiotherapy and concurrent docetaxel and cisplatin chemotherapy in driver-gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: A total of 72 NSCLC patients with brain metastases, who were treated in our hospital from June 2018 to June 2019, were enrolled in this study. The driver gene was proved to be negative by next generation sequencing (NGS). The patients were divided into control group (36 cases) and treatment group (36 cases) by Digital random grouping method.The control group received 2 cycles of chemotherapy with docetaxel and cisplatin and concurrent radiotherapy for brain metastases, and the treatment group was given Apatinib anti-angiogenic treatment based on the regimen in control group. Primary study endpoints: confirmed objective response rate (cORR) and disease control rate (DCR); Secondary study endpoints: progression-free survival (PFS), quality of life (QOL) score, serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), and incidence of adverse drug events (AE). Results: Compared with the control group, cORR and DCR in treatment group were significantly improved [41.67% (15/36) vs 33.33% (12/36), 80.56% (29/36) vs 69.44% (25/36), all P<0.05], the median PFS was significantly prolonged (5.9 vs 4.6 months, P<0.05), and serum CEA and VEGF levels were significantly reduced [(16.5±2.3) vs (22.9±3.7) ng/ml, (291.6±42.6) vs (479.3±50.2) ng/L, all P<0.05], while the QOL score was slightly increased, but the difference was not statistically significant [(69.5±8.5) points vs (64.1±7.3) points, P>0.05]. There was no statistically significant difference in the incidence of acute brain edema, gastrointestinal reaction, bone marrow suppression, and liver dysfunction between the two groups of patients (all P>0.05); however, the incidences of oral mucositis, hand-foot syndrome,hypertension and proteinuria in the treatment group were significantly higher than those in the control group (all P<0.05). Conclusion:The efficacy of Apatinib combined with radiochemotherapy in driver-negative NSCLC patients with brain metastases is significantly better than that of radiochemotherapy alone, and the adverse reactions can be controlled. It is worthy of clinical recommendation.
Objective: To observe the short-term efficacy and safety of Apatinib combined with radiotherapy and concurrent docetaxel and cisplatin chemotherapy in driver-gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: A total of 72 NSCLC patients with brain metastases, who were treated in our hospital from June 2018 to June 2019, were enrolled in this study. The driver gene was proved to be negative by next generation sequencing (NGS). The patients were divided into control group (36 cases) and treatment group (36 cases) by Digital random grouping method.The control group received 2 cycles of chemotherapy with docetaxel and cisplatin and concurrent radiotherapy for brain metastases, and the treatment group was given Apatinib anti-angiogenic treatment based on the regimen in control group. Primary study endpoints: confirmed objective response rate (cORR) and disease control rate (DCR); Secondary study endpoints: progression-free survival (PFS), quality of life (QOL) score, serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), and incidence of adverse drug events (AE). Results: Compared with the control group, cORR and DCR in treatment group were significantly improved [41.67% (15/36) vs 33.33% (12/36), 80.56% (29/36) vs 69.44% (25/36), all P<0.05], the median PFS was significantly prolonged (5.9 vs 4.6 months, P<0.05), and serum CEA and VEGF levels were significantly reduced [(16.5±2.3) vs (22.9±3.7) ng/ml, (291.6±42.6) vs (479.3±50.2) ng/L, all P<0.05], while the QOL score was slightly increased, but the difference was not statistically significant [(69.5±8.5) points vs (64.1±7.3) points, P>0.05]. There was no statistically significant difference in the incidence of acute brain edema, gastrointestinal reaction, bone marrow suppression, and liver dysfunction between the two groups of patients (all P>0.05); however, the incidences of oral mucositis, hand-foot syndrome,hypertension and proteinuria in the treatment group were significantly higher than those in the control group (all P<0.05). Conclusion:The efficacy of Apatinib combined with radiochemotherapy in driver-negative NSCLC patients with brain metastases is significantly better than that of radiochemotherapy alone, and the adverse reactions can be controlled. It is worthy of clinical recommendation.
2020, 27(6):664-670.
DOI: 10.3872/j.issn.1007-385X.2020.06.012
Abstract:
Objective: To investigate the effects of miR-223-3p on the proliferation and apoptosis of hepatocellular carcinoma (HCC)cells by regulating Ras-related C3 botulinum toxin substrate 1 (RAC1) and its possible mechanism. Methods: Thirty pairs of HCC and corresponding para-cancer tissues resected in Jilin Central Hospital from August 2016 to August 2018 were collected for this study; in addition, human HCC cell lines SMMC-7721, BEL-7402, HepG2 and human normal hepatocyte QSG-7701 were also collected. The expression level of miR-223-3p in HCC tissue and cell lines was detected by qPCR. miR-223-3p mimics, miR-223-3p inhibitor and siRAC1 were transfected into SMMC-7221 cells, respectively. CCK-8 assay, Colony formation assay and Annexin V-FITC/PI staining Flow cytometry were used to detect the proliferation, clone formation and apoptosis of SMMC-7721 cells, respectively. The relationship between miR-223-3p and RAC1 was confirmed by Dual luciferase reporter gene assay. The protein level of RAC1 in SMMC-7721 cells was detected by Western blotting. Results: The expression of miR-223-3p in HCC tissues was significantly lower than that in paracaner tissues (P<0.01), and had significant correlation with pathological characteristics, such as tumor size, TNM stage, Edmondson-Steiner grade (all P<0.05 or P<0.01). miR-223-3p expression in HCC cell lines was significantly lower than that in QSG-7701 cells with the lowest expression in SMMC-7721 cells. Dual luciferase reporter gene assay confirmed that RAC1 was a target gene of miR-223-3p, and miR-223-3p negatively regulated RAC1 expression. Over-expression of miR-223-3p significantly inhibited the proliferation and colony formation (P<0.05 or P<0.01) of SMMC-7721 cells and promoted cell apoptosis (P<0.01). Contrarily, knockdown of miR-223-3p reversed the inhibitory effect of miR-223-3p mimics on cells. Conclusion: miR-223-3p over-expression inhibits proliferation and colony formation and promotes apoptosis of HCC cells, the mechanism of which may be related with its targeted down-regulation of RAC1.
Objective: To investigate the effects of miR-223-3p on the proliferation and apoptosis of hepatocellular carcinoma (HCC)cells by regulating Ras-related C3 botulinum toxin substrate 1 (RAC1) and its possible mechanism. Methods: Thirty pairs of HCC and corresponding para-cancer tissues resected in Jilin Central Hospital from August 2016 to August 2018 were collected for this study; in addition, human HCC cell lines SMMC-7721, BEL-7402, HepG2 and human normal hepatocyte QSG-7701 were also collected. The expression level of miR-223-3p in HCC tissue and cell lines was detected by qPCR. miR-223-3p mimics, miR-223-3p inhibitor and siRAC1 were transfected into SMMC-7221 cells, respectively. CCK-8 assay, Colony formation assay and Annexin V-FITC/PI staining Flow cytometry were used to detect the proliferation, clone formation and apoptosis of SMMC-7721 cells, respectively. The relationship between miR-223-3p and RAC1 was confirmed by Dual luciferase reporter gene assay. The protein level of RAC1 in SMMC-7721 cells was detected by Western blotting. Results: The expression of miR-223-3p in HCC tissues was significantly lower than that in paracaner tissues (P<0.01), and had significant correlation with pathological characteristics, such as tumor size, TNM stage, Edmondson-Steiner grade (all P<0.05 or P<0.01). miR-223-3p expression in HCC cell lines was significantly lower than that in QSG-7701 cells with the lowest expression in SMMC-7721 cells. Dual luciferase reporter gene assay confirmed that RAC1 was a target gene of miR-223-3p, and miR-223-3p negatively regulated RAC1 expression. Over-expression of miR-223-3p significantly inhibited the proliferation and colony formation (P<0.05 or P<0.01) of SMMC-7721 cells and promoted cell apoptosis (P<0.01). Contrarily, knockdown of miR-223-3p reversed the inhibitory effect of miR-223-3p mimics on cells. Conclusion: miR-223-3p over-expression inhibits proliferation and colony formation and promotes apoptosis of HCC cells, the mechanism of which may be related with its targeted down-regulation of RAC1.
2020, 27(6):671-677.
DOI: 10.3872/j.issn.1007-385X.2020.06.013
Abstract:
Objective: To explore the clinical significance and in vitro biological effect of ubiquitin carboxyl-terminal hydrolase L5 (UCHL5)expression in thyroid carcinoma (TC) tissues. Methods: TCGA data were used to analyze the expression of UCHL5 in thyroid carcinoma tissues and its relationship with the prognosis of patients. 82 pairs of TC tissues and corresponding adjacent tissues were collected in the Department of Vascular and Thyroid Surgery, Sichuan Provincial People's Hospital from May 2018 to July 2019; TC cell lines (KTC-1 and WRO) were cultured in vitro, and transfected with UCHL5 overexpression vectors or their control vectors via lentivirus. The mRNA and protein expressions of UCHL5 and B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) in tissues and cells were detected by qPCR and Western blotting, respectively. Cell proliferation was detected by CCK-8, and cell invasion and migration were detected by Transwell and Wound-healing experiments. Results: The expression of UCHL5 was low in TC tissues (P<0.01), and its expression was upregulated in tumor tissues with high TNM stage (P<0.01). The expression of UCHL5 was significantly correlated with BRAF expression and TNM stage of patients (all P<0.01), but not significantly related with patient's age, gender, pathological type and BRAF mutation (all P>0.05).In vitro overexpression of UCHL5 in KTC-1 andWRO cells could significantly promote BRAF expression, cell proliferation and metastasis (all P<0.01). Conclusion: The expression of UCHL5 is low in TC tissue, but upregulated with tumor progression. The high expression of UCHL5 in TC patients suggests poor prognosis. Meanwhile, UCHL5 can promote the malignant behaviors of TC cells in vitro.
Objective: To explore the clinical significance and in vitro biological effect of ubiquitin carboxyl-terminal hydrolase L5 (UCHL5)expression in thyroid carcinoma (TC) tissues. Methods: TCGA data were used to analyze the expression of UCHL5 in thyroid carcinoma tissues and its relationship with the prognosis of patients. 82 pairs of TC tissues and corresponding adjacent tissues were collected in the Department of Vascular and Thyroid Surgery, Sichuan Provincial People's Hospital from May 2018 to July 2019; TC cell lines (KTC-1 and WRO) were cultured in vitro, and transfected with UCHL5 overexpression vectors or their control vectors via lentivirus. The mRNA and protein expressions of UCHL5 and B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) in tissues and cells were detected by qPCR and Western blotting, respectively. Cell proliferation was detected by CCK-8, and cell invasion and migration were detected by Transwell and Wound-healing experiments. Results: The expression of UCHL5 was low in TC tissues (P<0.01), and its expression was upregulated in tumor tissues with high TNM stage (P<0.01). The expression of UCHL5 was significantly correlated with BRAF expression and TNM stage of patients (all P<0.01), but not significantly related with patient's age, gender, pathological type and BRAF mutation (all P>0.05).In vitro overexpression of UCHL5 in KTC-1 andWRO cells could significantly promote BRAF expression, cell proliferation and metastasis (all P<0.01). Conclusion: The expression of UCHL5 is low in TC tissue, but upregulated with tumor progression. The high expression of UCHL5 in TC patients suggests poor prognosis. Meanwhile, UCHL5 can promote the malignant behaviors of TC cells in vitro.
2020, 27(6):678-684.
DOI: 10.3872/j.issn.1007-385X.2020.06.014
Abstract:
Objective: To identify the molecules related to the occurrence, development and prognosis of hepatocellular carcinoma (HCC) by constructing ceRNA regulatory network of HCC. Methods: Data of HCC transcription group were downloaded from TCGA database. We processed the original data into expression matrix of mRNA, lncRNA and miRNA via Perl language. DGEs of RNA and microRNA were extracted and analyzed from the“Edge”package of R language with the threshold of (|log FC|>2.0 and P<0.01).Through the database comparison, the relationship pairs of different lncRNAs-different miRNAs, different miRNAs-different mRNAs were obtained, and then imported them into the Cytoscape software to construct the ceRNA regulatory network diagram. The survival data of three DGEs were collected and analyzed by“survival”package and Kaplan Meier plotter analysis software. The survival curves were drawn and the genes were obtained by survival analysis. Results: The lncRNA related ceRNA regulatory network of HCC was successfully constructed. Three regulatory pairs of lncRNA-miRNA-mRNA were obtained by analyzing the interaction and regulatory relationship between DGEs via ceRNA network. Among them, one regulatory pathway (CCDC26-hsa-mir-141-EPHA2)was in accordance with ceRNA theory. The prognostic analyses showed that the survival rate of patients with high expression of 14 mRNAs was lower than those with low expression, which could be used as biomarkers of adverse prognosis of HCC. The survival rate of patients with low expression of 1 lncRNA (TSPEAR-AS1) and 2 mRNA (CPEB3 and PROK2) was lower than those with high expression, which may be the protective gene of HCC. Conclusions: Through screening of HCC lncRNA related ceRNA regulatory network, 14 mRNAs with high expression may be the relevant molecules related to poor prognosis of HCC, while 1 lncRNAand 2 mRNAs with low expression may be the molecules related to good prognosis of HCC, providing reference for HCC treatment and prognosis evaluation.
Objective: To identify the molecules related to the occurrence, development and prognosis of hepatocellular carcinoma (HCC) by constructing ceRNA regulatory network of HCC. Methods: Data of HCC transcription group were downloaded from TCGA database. We processed the original data into expression matrix of mRNA, lncRNA and miRNA via Perl language. DGEs of RNA and microRNA were extracted and analyzed from the“Edge”package of R language with the threshold of (|log FC|>2.0 and P<0.01).Through the database comparison, the relationship pairs of different lncRNAs-different miRNAs, different miRNAs-different mRNAs were obtained, and then imported them into the Cytoscape software to construct the ceRNA regulatory network diagram. The survival data of three DGEs were collected and analyzed by“survival”package and Kaplan Meier plotter analysis software. The survival curves were drawn and the genes were obtained by survival analysis. Results: The lncRNA related ceRNA regulatory network of HCC was successfully constructed. Three regulatory pairs of lncRNA-miRNA-mRNA were obtained by analyzing the interaction and regulatory relationship between DGEs via ceRNA network. Among them, one regulatory pathway (CCDC26-hsa-mir-141-EPHA2)was in accordance with ceRNA theory. The prognostic analyses showed that the survival rate of patients with high expression of 14 mRNAs was lower than those with low expression, which could be used as biomarkers of adverse prognosis of HCC. The survival rate of patients with low expression of 1 lncRNA (TSPEAR-AS1) and 2 mRNA (CPEB3 and PROK2) was lower than those with high expression, which may be the protective gene of HCC. Conclusions: Through screening of HCC lncRNA related ceRNA regulatory network, 14 mRNAs with high expression may be the relevant molecules related to poor prognosis of HCC, while 1 lncRNAand 2 mRNAs with low expression may be the molecules related to good prognosis of HCC, providing reference for HCC treatment and prognosis evaluation.
2020, 27(6):685-690.
DOI: 10.3872/j.issn.1007-385X.2020.06.015
Abstract:
乳腺癌是全世界女性发病率最高的恶性肿瘤之一，尽管在经过手术、化疗、放疗、内分泌药物及分子靶向药物等系统治疗后大部分患者能长期生存，甚至治愈，但仍有30%~40%的患者可能复发转移。近年来，晚期乳腺癌的综合治疗取得了长足的进步，主要是由于一系列新药的诞生，特别是内分泌和靶向治疗药物，其中免疫检查点抑制剂开启了全新的抗肿瘤治疗模式，被认为是十分有效而免疫相关不良反应最小的免疫治疗方法，已经成为国内外肿瘤治疗领域中颇具研究前景的方向之一。
乳腺癌是全世界女性发病率最高的恶性肿瘤之一，尽管在经过手术、化疗、放疗、内分泌药物及分子靶向药物等系统治疗后大部分患者能长期生存，甚至治愈，但仍有30%~40%的患者可能复发转移。近年来，晚期乳腺癌的综合治疗取得了长足的进步，主要是由于一系列新药的诞生，特别是内分泌和靶向治疗药物，其中免疫检查点抑制剂开启了全新的抗肿瘤治疗模式，被认为是十分有效而免疫相关不良反应最小的免疫治疗方法，已经成为国内外肿瘤治疗领域中颇具研究前景的方向之一。
2020, 27(6):691-697.
DOI: 10.3872/j.issn.1007-385X.2020.06.016
Abstract:
免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）越来越广泛地应用于癌症治疗当中，其中程序性细胞死亡蛋白-1（programmed cell death-1，PD-1）抑制剂疗效显著，能够延长肿瘤患者总生存期，是目前研究最多发展最快的免疫检查点抑制剂。然而，PD-1 抑制剂也会引起免疫相关性不良反应，肝脏毒性便是其中较为常见的一种。本文将对PD-1 抑制剂癌症治疗中肝脏毒性的特点、诊断及治疗原则、预后等方面进行综述，为临床的诊断和治疗提供依据。
免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）越来越广泛地应用于癌症治疗当中，其中程序性细胞死亡蛋白-1（programmed cell death-1，PD-1）抑制剂疗效显著，能够延长肿瘤患者总生存期，是目前研究最多发展最快的免疫检查点抑制剂。然而，PD-1 抑制剂也会引起免疫相关性不良反应，肝脏毒性便是其中较为常见的一种。本文将对PD-1 抑制剂癌症治疗中肝脏毒性的特点、诊断及治疗原则、预后等方面进行综述，为临床的诊断和治疗提供依据。
2020, 27(6):698-704.
DOI: 10.3872/j.issn.1007-385X.2020.06.017
Abstract:
随着免疫学及分子生物学的发展，免疫治疗已成为抗肿瘤治疗的一种新模式。特别是免疫检查点抑制剂的临床应用日益广泛，并在多种实体瘤治疗中展现出优良前景，被视为最具有潜力抗肿瘤治疗方式之一。但越来越多的证据提示，免疫治疗产生了不同于传统应答模式的非常规免疫反应模式，包括假性进展、延迟反应等；同时研究证实，传统的实体瘤治疗疗效评价标准往往无法准确捕捉此类非常规反应，从而难以正确评估免疫治疗疗效，这为临床工作带来了极大困扰与挑战。因此，新的实体瘤免疫治疗疗效评价标准亟待建立与完善，导致一系列免疫相关疗效评价标准被陆续提出。本文就实体瘤免疫治疗，主要是检查点抑制剂治疗的非常规反应模式及相关疗效评价标准研究发展和应用作一综述。
随着免疫学及分子生物学的发展，免疫治疗已成为抗肿瘤治疗的一种新模式。特别是免疫检查点抑制剂的临床应用日益广泛，并在多种实体瘤治疗中展现出优良前景，被视为最具有潜力抗肿瘤治疗方式之一。但越来越多的证据提示，免疫治疗产生了不同于传统应答模式的非常规免疫反应模式，包括假性进展、延迟反应等；同时研究证实，传统的实体瘤治疗疗效评价标准往往无法准确捕捉此类非常规反应，从而难以正确评估免疫治疗疗效，这为临床工作带来了极大困扰与挑战。因此，新的实体瘤免疫治疗疗效评价标准亟待建立与完善，导致一系列免疫相关疗效评价标准被陆续提出。本文就实体瘤免疫治疗，主要是检查点抑制剂治疗的非常规反应模式及相关疗效评价标准研究发展和应用作一综述。
2020, 27(6):705-710.
DOI: 10.3872/j.issn.1007-385X.2020.06.018
Abstract:
近年来，肿瘤免疫疗法已逐渐成为继手术、化疗、放疗之后的第四大肿瘤治疗手段。作为肿瘤免疫疗法之一的溶瘤病毒疗法，在沉寂了多年之后，再次成为关注的焦点。溶瘤病毒主要通过选择性杀伤肿瘤细胞和诱导机体产生特异性抗肿瘤免疫应答两种途径来实现肿瘤靶向治疗的目的，从而达到较好的抗肿瘤效果。更重要的是，当其与化疗药物、放疗、免疫检查点抑制剂、CAR-T细胞等疗法联合应用时，具有协同效应，进一步提高肿瘤治疗的效果，有着巨大的应用前景，有望成为未来肿瘤治疗的新方向。本文从常用的溶瘤病毒及其机制、临床应用现状、联合治疗和展望等方面进行综述。
近年来，肿瘤免疫疗法已逐渐成为继手术、化疗、放疗之后的第四大肿瘤治疗手段。作为肿瘤免疫疗法之一的溶瘤病毒疗法，在沉寂了多年之后，再次成为关注的焦点。溶瘤病毒主要通过选择性杀伤肿瘤细胞和诱导机体产生特异性抗肿瘤免疫应答两种途径来实现肿瘤靶向治疗的目的，从而达到较好的抗肿瘤效果。更重要的是，当其与化疗药物、放疗、免疫检查点抑制剂、CAR-T细胞等疗法联合应用时，具有协同效应，进一步提高肿瘤治疗的效果，有着巨大的应用前景，有望成为未来肿瘤治疗的新方向。本文从常用的溶瘤病毒及其机制、临床应用现状、联合治疗和展望等方面进行综述。
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- 《中国肿瘤生物治疗杂志》
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.