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Volume 27,Issue 11,2020 Table of Contents
2020, 27(11):1199-1205.
DOI: 10.3872/j.issn.1007-385X.2020.11.001
Abstract:
Thyroid cancer is a common endocrine malignant tumor, and its incidence is increasing year by year. Understanding the pathogenesis of thyroid cancer is essential for improving the accuracy of diagnosis, precise risk stratification, and the realization of personalized treatment. Recently, with the consistent development of mass spectrometry-related technologies, a variety of proteomics analysis methods based on different specimen types (cells, tissues, serum and urine) have been widely used in the research of thyroid cancer, thereby actively promote the development of precision diagnosis and treatment of thyroid cancer through elucidating the pathogenesis, diagnostic classification, prognosis prediction and targeted therapy etc.
Thyroid cancer is a common endocrine malignant tumor, and its incidence is increasing year by year. Understanding the pathogenesis of thyroid cancer is essential for improving the accuracy of diagnosis, precise risk stratification, and the realization of personalized treatment. Recently, with the consistent development of mass spectrometry-related technologies, a variety of proteomics analysis methods based on different specimen types (cells, tissues, serum and urine) have been widely used in the research of thyroid cancer, thereby actively promote the development of precision diagnosis and treatment of thyroid cancer through elucidating the pathogenesis, diagnostic classification, prognosis prediction and targeted therapy etc.
2020, 27(11):1206-1212.
DOI: 10.3872/j.issn.1007-385X.2020.11.002
Abstract:
Objective: To investigate the effect of miR-202-5p on the viability, colony formation, migration and invasion of oral squamous cell carcinoma (OSCC) cells, and to elucidate its possible mechanism. Methods: The mRNA expression levels of miR-202-5p and nuclear factor of activated T-cells isoform c3 (NFATc3) in OSCC cell lines(Tca8113 and SCC-4) were detected by qPCR. miR-202-5p mimics or/and NFATc3 overexpression plasmids were transfected into Tca8113 cells and SCC-4 cells. Cell proliferation was detected by MTT assay and colony formation assay; cell migration and invasion were detected by Wound-healing assay and Transwell assay; the expression level of NFATc3 protein was detected by Western blotting. The direct regulation of miR-202-5p on the candidate target gene NFATc3 was verified by Dual luciferase reporter gene assay. Results: Compared with the normal oral keratinocytes HOK, the expression level of miR-202-5p was significantly decreased in OSCC cell lines (P<0.01), and the mRNA and protein expressions of NFATc3 were significantly increased (P<0.01). Over-expression of miR-202-5p significantly inhibited cell viability, colony formation,migration, invasion, and the expression level of NFATc3 in Tca8113 cells and SCC-4 cells (all P<0.01). NFATc3 was proved to be a target gene of miR-202-5p. Over-expression of NFATc3 could reverse the inhibitory effect of miR-202-5p on the growth, migration and invasion of OSCC cells. Conclusion: miR-202-5p exerts its tumor suppressor function by down-regulating NFATc3 directly, leading to the inhibition of growth, migration and invasion of OSCC cells.
Objective: To investigate the effect of miR-202-5p on the viability, colony formation, migration and invasion of oral squamous cell carcinoma (OSCC) cells, and to elucidate its possible mechanism. Methods: The mRNA expression levels of miR-202-5p and nuclear factor of activated T-cells isoform c3 (NFATc3) in OSCC cell lines(Tca8113 and SCC-4) were detected by qPCR. miR-202-5p mimics or/and NFATc3 overexpression plasmids were transfected into Tca8113 cells and SCC-4 cells. Cell proliferation was detected by MTT assay and colony formation assay; cell migration and invasion were detected by Wound-healing assay and Transwell assay; the expression level of NFATc3 protein was detected by Western blotting. The direct regulation of miR-202-5p on the candidate target gene NFATc3 was verified by Dual luciferase reporter gene assay. Results: Compared with the normal oral keratinocytes HOK, the expression level of miR-202-5p was significantly decreased in OSCC cell lines (P<0.01), and the mRNA and protein expressions of NFATc3 were significantly increased (P<0.01). Over-expression of miR-202-5p significantly inhibited cell viability, colony formation,migration, invasion, and the expression level of NFATc3 in Tca8113 cells and SCC-4 cells (all P<0.01). NFATc3 was proved to be a target gene of miR-202-5p. Over-expression of NFATc3 could reverse the inhibitory effect of miR-202-5p on the growth, migration and invasion of OSCC cells. Conclusion: miR-202-5p exerts its tumor suppressor function by down-regulating NFATc3 directly, leading to the inhibition of growth, migration and invasion of OSCC cells.
2020, 27(11):1213-1219.
DOI: 10.3872/j.issn.1007-385X.2020.11.003
Abstract:
Objective：To investigate the effects of RNA interfering NEK2 (NIMA-related kinase 2) gene on the sensitivity of colorectal carcinoma (CRC) cell lines to 5-fluorouracil (5-FU) and the possible mechanisms. Methods: The mRNA and protein expressions of NEK2 in CRC cell lines were detected by quantitative polymerase chain reaction (qPCR) and Western blotting assay,respectively. siRNAs targeting NEK2 were constructed and transfected into CRC HCT116 and SW620 cells. The experiments were divided into positive interference group 1 (transfection with NEK2 siRNA1), positive interference group 2 (transfection with NEK2 siRNA2) and negative control group (transfection with si-NC), all the CRC cells were treated with 5-FU. CCK-8 assay, Flow cytometry and V-FICT/PI Annexin staining analysis were used to observe the effects of NEK2 gene knockdown on proliferation, cell cycle distribution and apoptosis of CRC cells under 5-FU treatment. Western blotting was used to detect the effects of NEK2 gene knockdown on the expression of Wnt/β-catenin signaling pathway related proteins in CRC cells under 5-FU treatment. Results: NEK2 was highly expressed in CRC HCT116 and SW620 cells at both protein and mRNA levels (all P<0.05). siRNA NEK2 transfection could effectively inhibit the protein and mRNA expressions of NEK2 in HCT116 and SW620 cells (all P<0.01). After treatment with various concentrations of 5-FU, the cell survival rate and IC50, as well as the expression levels of β-catenin (cytoblasts), C-MYC and Cyclin D1,in the positive interference group 1 and 2 were significantly decreased, while cell cycle blockage at G0/G1 phase, the apoptosis rate and the expression level of β-catenin (cytoplasm) were significantly increased (all P<0.01), as compared with the negative control group (all P<0.01). Conclusion: Silencing NEK2 gene can effectively improve the sensitivity of human colorectal cancer cells to 5-FU, which may be achieved by regulating the expression of Wnt/β-catenin signaling pathway related proteins.
Objective：To investigate the effects of RNA interfering NEK2 (NIMA-related kinase 2) gene on the sensitivity of colorectal carcinoma (CRC) cell lines to 5-fluorouracil (5-FU) and the possible mechanisms. Methods: The mRNA and protein expressions of NEK2 in CRC cell lines were detected by quantitative polymerase chain reaction (qPCR) and Western blotting assay,respectively. siRNAs targeting NEK2 were constructed and transfected into CRC HCT116 and SW620 cells. The experiments were divided into positive interference group 1 (transfection with NEK2 siRNA1), positive interference group 2 (transfection with NEK2 siRNA2) and negative control group (transfection with si-NC), all the CRC cells were treated with 5-FU. CCK-8 assay, Flow cytometry and V-FICT/PI Annexin staining analysis were used to observe the effects of NEK2 gene knockdown on proliferation, cell cycle distribution and apoptosis of CRC cells under 5-FU treatment. Western blotting was used to detect the effects of NEK2 gene knockdown on the expression of Wnt/β-catenin signaling pathway related proteins in CRC cells under 5-FU treatment. Results: NEK2 was highly expressed in CRC HCT116 and SW620 cells at both protein and mRNA levels (all P<0.05). siRNA NEK2 transfection could effectively inhibit the protein and mRNA expressions of NEK2 in HCT116 and SW620 cells (all P<0.01). After treatment with various concentrations of 5-FU, the cell survival rate and IC50, as well as the expression levels of β-catenin (cytoblasts), C-MYC and Cyclin D1,in the positive interference group 1 and 2 were significantly decreased, while cell cycle blockage at G0/G1 phase, the apoptosis rate and the expression level of β-catenin (cytoplasm) were significantly increased (all P<0.01), as compared with the negative control group (all P<0.01). Conclusion: Silencing NEK2 gene can effectively improve the sensitivity of human colorectal cancer cells to 5-FU, which may be achieved by regulating the expression of Wnt/β-catenin signaling pathway related proteins.
2020, 27(11):1220-1228.
DOI: 10.3872/j.issn.1007-385X.2020.11.004
Abstract:
Objective: To investigate the role of circRNA_001569 in the proliferation, invasion and migration of breast cancer cells via miR-145/HBXIP axis. Methods: Collected 30 cases of cancerous tissue and 30 adjacent tissues of breast cancer patients treated in the Hengshui People's Hospital from January 2016 to January 2019. qPCR detects the expression of circRNA_001569 in breast cancer tissues, adjacent tissues and cell lines. Bioinformatics tools were used to predict the target genes of miR-145. RNA immunoprecipitation (RIP) and Dual luciferase reporter gene assay were used to detect the interaction between genes or proteins. si-circRNA_001569,miR-145 mimics or miR-145 inhibitor were transfected into breast cancer MDA-MB-231 and MCF-7 cells to establish gene overexpression or silence cell models. qPCR and Western blotting were used to detect the expressions of related genes and proteins.CCK-8 method and Transwell test were used to detect the proliferation, invasion and migration of transfected cells. Results: In breast cancer tissues and breast cancer cells, the expressions of circRNA_001569 and HBXIP were up-regulated, while the expression of miR-145 was down-regulated; RIP analysis and Dual luciferase analysis revealed the targeting relationship among miR-145,circRNA_001569 and HBXIP. Over-expression of circRNA_001569 or HBXIP promoted the proliferation, invasion and migration of MDA-MB-231 and MCF-7 cells (all P<0.01), while miR-145 overexpression had the opposite effect (all P<0.01). Conclusion:circRNA_001569 may promote the proliferation, invasion and migration of breast cancer cells by down-regulating the expression of miR-145 and up-regulating the expression of HBXIP.
Objective: To investigate the role of circRNA_001569 in the proliferation, invasion and migration of breast cancer cells via miR-145/HBXIP axis. Methods: Collected 30 cases of cancerous tissue and 30 adjacent tissues of breast cancer patients treated in the Hengshui People's Hospital from January 2016 to January 2019. qPCR detects the expression of circRNA_001569 in breast cancer tissues, adjacent tissues and cell lines. Bioinformatics tools were used to predict the target genes of miR-145. RNA immunoprecipitation (RIP) and Dual luciferase reporter gene assay were used to detect the interaction between genes or proteins. si-circRNA_001569,miR-145 mimics or miR-145 inhibitor were transfected into breast cancer MDA-MB-231 and MCF-7 cells to establish gene overexpression or silence cell models. qPCR and Western blotting were used to detect the expressions of related genes and proteins.CCK-8 method and Transwell test were used to detect the proliferation, invasion and migration of transfected cells. Results: In breast cancer tissues and breast cancer cells, the expressions of circRNA_001569 and HBXIP were up-regulated, while the expression of miR-145 was down-regulated; RIP analysis and Dual luciferase analysis revealed the targeting relationship among miR-145,circRNA_001569 and HBXIP. Over-expression of circRNA_001569 or HBXIP promoted the proliferation, invasion and migration of MDA-MB-231 and MCF-7 cells (all P<0.01), while miR-145 overexpression had the opposite effect (all P<0.01). Conclusion:circRNA_001569 may promote the proliferation, invasion and migration of breast cancer cells by down-regulating the expression of miR-145 and up-regulating the expression of HBXIP.
2020, 27(11):1229-1238.
DOI: 10.3872/j.issn.1007-385X.2020.11.005
Abstract:
Objective: The phosphorproteomics technique was used to analyze the differential expression of phosphorylated proteins in the human lung adenocarcinoma A549 cells treated with antimicrobial peptide merecidin, and to explore the effect of merecidin on the protein activity and function of lung adenocarcinoma A549 cells and the signal pathway involved. Methods: A549 cells were treated with 9 μmol/L merecidin for 6 h. The total protein was collected and extracted, and SDS-PAGE experiment was used to test the total protein extraction efficiency. Pancreatin was added to digest the protein. The peptides obtained by enzymatic hydrolysis were labeled with TMT,fractionated by HPLC, enriching phosphorylated modified peptides by IMAC, and separate peptides by HPLC-MS/MS (liquid chromatographymass spectrometry) technology. The identified data were screened using the standard of localization probability>0.75, and the phosphoproteomics data were analyzed using GO (Gene Ontology) database, KEGG (Kyoto Encyclopedia of Genes and Genomes) database and STRING database. Results: SDS-PAGE results showed that the total protein separation of A549 cells treated with 9 μmol/L merecidin was clear and no obvious degradation, and there was significant difference in protein bands between the experimental group and the control group.A total of 10 320 phosphorylation modification sites on 3 089 proteins were identified by mass spectrometry, of which 753 proteins and 1 172 phosphorylation sites were screened out with |Fold Change| >1.5 and P<0.05 as the threshold. Protein function enrichment showed that functions of proteins with significant changes in phosphorylation level mainly focused on molecular binding, metabolic activity, molecular function regulation, cell process, biological function and other aspects. Bioinformatics results of integrated pathway showed that differentially expressed proteins were associated with Ras, PI3K/AKT, mTor, AMPK etc. COG database screening showed that the differentially expressed phosphorylated proteins were concentrated in cell signal transduction, processing and modification of RNA transcription and translation,protein synthesis of ribosome, formation of cytoskeleton proteins, intracellular substance transportation, secretion and vesicle transportation etc. At the protein interaction level, after merecidin treatment, an interaction network with MAPK1, RPL23A, SRSF3H, NCBP1, etc. as key proteins was formed in A549 cells; proteins such as ATG2B and ULK1 etc. were significantly up-regulated, while proteins such as MAPK1 and AKT1 etc. were significantly down-regulated. Conclusion: Phosphoproteomic analysis shows that the antimicrobial peptide merecidin may play a role in multiple biological functions and multiple signaling pathways through key proteins such as MAPK1, RPL23A, SRSF3H and AKT1, and promote the apoptosis and autophagy of lung adenocarcinoma A549 cells, thereby inhibiting cell proliferation.
Objective: The phosphorproteomics technique was used to analyze the differential expression of phosphorylated proteins in the human lung adenocarcinoma A549 cells treated with antimicrobial peptide merecidin, and to explore the effect of merecidin on the protein activity and function of lung adenocarcinoma A549 cells and the signal pathway involved. Methods: A549 cells were treated with 9 μmol/L merecidin for 6 h. The total protein was collected and extracted, and SDS-PAGE experiment was used to test the total protein extraction efficiency. Pancreatin was added to digest the protein. The peptides obtained by enzymatic hydrolysis were labeled with TMT,fractionated by HPLC, enriching phosphorylated modified peptides by IMAC, and separate peptides by HPLC-MS/MS (liquid chromatographymass spectrometry) technology. The identified data were screened using the standard of localization probability>0.75, and the phosphoproteomics data were analyzed using GO (Gene Ontology) database, KEGG (Kyoto Encyclopedia of Genes and Genomes) database and STRING database. Results: SDS-PAGE results showed that the total protein separation of A549 cells treated with 9 μmol/L merecidin was clear and no obvious degradation, and there was significant difference in protein bands between the experimental group and the control group.A total of 10 320 phosphorylation modification sites on 3 089 proteins were identified by mass spectrometry, of which 753 proteins and 1 172 phosphorylation sites were screened out with |Fold Change| >1.5 and P<0.05 as the threshold. Protein function enrichment showed that functions of proteins with significant changes in phosphorylation level mainly focused on molecular binding, metabolic activity, molecular function regulation, cell process, biological function and other aspects. Bioinformatics results of integrated pathway showed that differentially expressed proteins were associated with Ras, PI3K/AKT, mTor, AMPK etc. COG database screening showed that the differentially expressed phosphorylated proteins were concentrated in cell signal transduction, processing and modification of RNA transcription and translation,protein synthesis of ribosome, formation of cytoskeleton proteins, intracellular substance transportation, secretion and vesicle transportation etc. At the protein interaction level, after merecidin treatment, an interaction network with MAPK1, RPL23A, SRSF3H, NCBP1, etc. as key proteins was formed in A549 cells; proteins such as ATG2B and ULK1 etc. were significantly up-regulated, while proteins such as MAPK1 and AKT1 etc. were significantly down-regulated. Conclusion: Phosphoproteomic analysis shows that the antimicrobial peptide merecidin may play a role in multiple biological functions and multiple signaling pathways through key proteins such as MAPK1, RPL23A, SRSF3H and AKT1, and promote the apoptosis and autophagy of lung adenocarcinoma A549 cells, thereby inhibiting cell proliferation.
2020, 27(11):1239-1245.
DOI: 10.3872/j.issn.1007-385X.2020.11.006
Abstract:
Objective: To investigate the effects of overexpressed miR-497 targeting cyclin E1 (CCNE1) on epithelial-mesenchymal transition (EMT) in lung cancer A549 cells. Methods：Human lung cancer A549 cells were routinely cultured, and the experimental cells were divided into normal group (without any intervention), control group (transfected with miR-497 mimics-NC), and experiment group (transfected with miR-497 mimics). Transwell chamber experiment, immunofluorescence staining, qPCR, Western blotting were used to detect cell migration and invasion ability, the expressions of protein interstitial marker α -SMA and epithelial marker E-cadherin, and the expressions of miR-497 and CCNE1 in each group of cells, respectively. Dual luciferase reporter gene assay was used to verify the relationship between miR-497 and CCNE1. Results: Compared with the normal group, the number of migrated and invaded cells in the experiment group decreased significantly (all P<0.05), the green fluorescence intensity of the interstitial marker α-SMA of the experimental group cells was significantly weakened [(36.95±5.81) vs (98.69±2.36), (97.94±2.63), all P<0.05], while the green fluorescence intensity of the epithelium marker E-cadherin was significantly enhanced [(388.41±10.93) vs (100.95±6.37),(102.55±3.18), all P<0.05]; in addition, the expression of miR-497 in the cells of the experiment group was significantly increased (all P<0.05), while theexpression of CCNE1 was significantly decreased (all P<0.05). miR-497 could targetedly regulate the expression of CCNE1. Conclusion: In lung cancer A549 cells, miR-497 can targetedly regulate CCNE1 expression. Up-regulating the expression of miR-497 can significantly inhibit the migration and invasion ability of A549 cells and affect the expression of EMT related protein.
Objective: To investigate the effects of overexpressed miR-497 targeting cyclin E1 (CCNE1) on epithelial-mesenchymal transition (EMT) in lung cancer A549 cells. Methods：Human lung cancer A549 cells were routinely cultured, and the experimental cells were divided into normal group (without any intervention), control group (transfected with miR-497 mimics-NC), and experiment group (transfected with miR-497 mimics). Transwell chamber experiment, immunofluorescence staining, qPCR, Western blotting were used to detect cell migration and invasion ability, the expressions of protein interstitial marker α -SMA and epithelial marker E-cadherin, and the expressions of miR-497 and CCNE1 in each group of cells, respectively. Dual luciferase reporter gene assay was used to verify the relationship between miR-497 and CCNE1. Results: Compared with the normal group, the number of migrated and invaded cells in the experiment group decreased significantly (all P<0.05), the green fluorescence intensity of the interstitial marker α-SMA of the experimental group cells was significantly weakened [(36.95±5.81) vs (98.69±2.36), (97.94±2.63), all P<0.05], while the green fluorescence intensity of the epithelium marker E-cadherin was significantly enhanced [(388.41±10.93) vs (100.95±6.37),(102.55±3.18), all P<0.05]; in addition, the expression of miR-497 in the cells of the experiment group was significantly increased (all P<0.05), while theexpression of CCNE1 was significantly decreased (all P<0.05). miR-497 could targetedly regulate the expression of CCNE1. Conclusion: In lung cancer A549 cells, miR-497 can targetedly regulate CCNE1 expression. Up-regulating the expression of miR-497 can significantly inhibit the migration and invasion ability of A549 cells and affect the expression of EMT related protein.
2020, 27(11):1246-1254.
DOI: 10.3872/j.issn.1007-385X.2020.11.007
Abstract:
Objective: To screen the differentially expressed gene (DEGs) and to identify potential diagnostic/prognostic markers as well as drug resistance markers in prostate cancer (PC) by bioinformatics analysis of published microarray data sets. Methods:Differential expression analyses were performed in available mRNA microarray datasets including prostate cancer tissues dataset GSE6956 and prostate cancer cell taxotere resistance dataset GSE33455 from the GEO database. Gene Ontology enrichment analysis (GO), gene pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed to identify the biological function and signaling pathways related to DEGs. The expression level of DEGs in PC tissues and para-cancerous tissues was verified by comparing TCGA datasets. Kaplan-Meier method was adopted to detect the influence of DEGs on the survival of PC patients. The expression of DEGs in PC3 cells and taxotere resistant PC3-DTX cells was detected by qPCR. Results: There were a total of 227 genes that differentially co-expressed in taxotere resistant prostate cancer cells and prostate cancer tissues. The functional enrichment analysis showed that these differentially co-expressed genes were mainly enriched in cancer related pathways (Lysosome,Sphingolipid, FoxO, Acute myeloid leukemia) and involved in cell-cell adhesion, autophagy and intracellular protein transportation etc.PPI network screened 18 most connected genes as Hub genes. Among the Hub genes and differentially co-expressed genes, the upregulated CITED2, LRP12 and RPL17-C18orf32 were significantly associated with poor outcomes of PC patients. qPCR validated that CITED2 was upregulated in PC3 and PC3-DTX cells. Conclusion: The present study identified a number of DEGs that differentially co-expressed in prostate cancer tissues and drug resistance cells and significantly associated with the poor prognosis of PC patients by bioinformatical analysis. These results may provide a new idea for identifying potential diagnostic/prognostic and drug resistant markers for prostate cancer.
Objective: To screen the differentially expressed gene (DEGs) and to identify potential diagnostic/prognostic markers as well as drug resistance markers in prostate cancer (PC) by bioinformatics analysis of published microarray data sets. Methods:Differential expression analyses were performed in available mRNA microarray datasets including prostate cancer tissues dataset GSE6956 and prostate cancer cell taxotere resistance dataset GSE33455 from the GEO database. Gene Ontology enrichment analysis (GO), gene pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed to identify the biological function and signaling pathways related to DEGs. The expression level of DEGs in PC tissues and para-cancerous tissues was verified by comparing TCGA datasets. Kaplan-Meier method was adopted to detect the influence of DEGs on the survival of PC patients. The expression of DEGs in PC3 cells and taxotere resistant PC3-DTX cells was detected by qPCR. Results: There were a total of 227 genes that differentially co-expressed in taxotere resistant prostate cancer cells and prostate cancer tissues. The functional enrichment analysis showed that these differentially co-expressed genes were mainly enriched in cancer related pathways (Lysosome,Sphingolipid, FoxO, Acute myeloid leukemia) and involved in cell-cell adhesion, autophagy and intracellular protein transportation etc.PPI network screened 18 most connected genes as Hub genes. Among the Hub genes and differentially co-expressed genes, the upregulated CITED2, LRP12 and RPL17-C18orf32 were significantly associated with poor outcomes of PC patients. qPCR validated that CITED2 was upregulated in PC3 and PC3-DTX cells. Conclusion: The present study identified a number of DEGs that differentially co-expressed in prostate cancer tissues and drug resistance cells and significantly associated with the poor prognosis of PC patients by bioinformatical analysis. These results may provide a new idea for identifying potential diagnostic/prognostic and drug resistant markers for prostate cancer.
2020, 27(11):1255-1263.
DOI: 10.3872/j.issn.1007-385X.2020.11.008
Abstract:
Objective: To detect the expression of long non-coding RNA (lncRNA) ARHGAP5-AS1 in breast cancer (BC) tissues and cell lines, analyze its relationship with the clinicopathological parameters and prognosis of BC patients, and to investigate its effect on the proliferation, migration and invasion of BC cells in vitro. Methods: LncRNA ARHGAP5-AS1 that low expressed in BC and associated with poor prognosis was screened out by bioinformatics analysis of BC-related data sets in TCGA database. qPCR was used to verify the expression of lncRNA ARHGAP5-AS1 in BC tissues collected from April 2010 to October 2016 in the Department of Oncology, Affiliated Hospital of Jiangnan University. χ2 test was used to analyze the relationship between the expression of ARHGAP5-AS1 and the clinicopathological parameters of BC patients. Kaplan-Meier survival analysis was performed to construct a survival curve to compare the overall and recurrence-free survival of the high and low expression groups. The effects of ARHGAP5-AS1 knockdown on the proliferation, migration and invasion of MDA-MB-231 and BT-549 cells were examined by CCK-8, Wound-healing assay and Transwell assay. Results: TCGA database analysis showed that the expression level of ARHGAP5-AS1 in BC tissues was significantly lower than that in normal breast tissues (P<0.01), and its low expression was significantly related to larger tumor diameter (T3), distant metastasis (M1), negative ER and PR, and shorter overall survival (all P<0.05). ARHGAP5-AS1 expression was significantly down-regulated in BC tissues compared with adjacent specimens (P<0.05), which was significantly associated with larger tumor diameter and lymph node metastasis (all P<0.05) in BC patients. Furthermore, ARHGAP5-AS1 was also reduced in 6 BC cell lines (MDA-MB-231, BT-549, MDA-MB-468, MCF-7, HCC1937, Hs578T) compared with normal breast epithelial cell line MCF-10A (all P<0.05). Cell function experiments showed that ARHGAP5-AS1 knockdown promoted proliferation, migration and invasion of MDA-MB-231 and BT-549 cells (all P<0.05). Conclusion: The abnormally low expression of ARHGAP5-AS1 may affect the occurrence and development of breast cancer by promoting the proliferation, migration and invasion of breast cancer cells.
Objective: To detect the expression of long non-coding RNA (lncRNA) ARHGAP5-AS1 in breast cancer (BC) tissues and cell lines, analyze its relationship with the clinicopathological parameters and prognosis of BC patients, and to investigate its effect on the proliferation, migration and invasion of BC cells in vitro. Methods: LncRNA ARHGAP5-AS1 that low expressed in BC and associated with poor prognosis was screened out by bioinformatics analysis of BC-related data sets in TCGA database. qPCR was used to verify the expression of lncRNA ARHGAP5-AS1 in BC tissues collected from April 2010 to October 2016 in the Department of Oncology, Affiliated Hospital of Jiangnan University. χ2 test was used to analyze the relationship between the expression of ARHGAP5-AS1 and the clinicopathological parameters of BC patients. Kaplan-Meier survival analysis was performed to construct a survival curve to compare the overall and recurrence-free survival of the high and low expression groups. The effects of ARHGAP5-AS1 knockdown on the proliferation, migration and invasion of MDA-MB-231 and BT-549 cells were examined by CCK-8, Wound-healing assay and Transwell assay. Results: TCGA database analysis showed that the expression level of ARHGAP5-AS1 in BC tissues was significantly lower than that in normal breast tissues (P<0.01), and its low expression was significantly related to larger tumor diameter (T3), distant metastasis (M1), negative ER and PR, and shorter overall survival (all P<0.05). ARHGAP5-AS1 expression was significantly down-regulated in BC tissues compared with adjacent specimens (P<0.05), which was significantly associated with larger tumor diameter and lymph node metastasis (all P<0.05) in BC patients. Furthermore, ARHGAP5-AS1 was also reduced in 6 BC cell lines (MDA-MB-231, BT-549, MDA-MB-468, MCF-7, HCC1937, Hs578T) compared with normal breast epithelial cell line MCF-10A (all P<0.05). Cell function experiments showed that ARHGAP5-AS1 knockdown promoted proliferation, migration and invasion of MDA-MB-231 and BT-549 cells (all P<0.05). Conclusion: The abnormally low expression of ARHGAP5-AS1 may affect the occurrence and development of breast cancer by promoting the proliferation, migration and invasion of breast cancer cells.
2020, 27(11):1264-1271.
DOI: 10.3872/j.issn.1007-385X.2020.11.009
Abstract:
Objective: To explore the metabolic differences between papillary thyroid carcinoma (PTC) tissues and adjacent tissues using tissue metabolomics methods, and to search for potential biomarkers of PTC as well as to explore the pathogenesis and treatment strategies for PTC. Methods: Collected cancer and para-cancerous tissue specim ens from 40 patients with PTC who had undergone breast surgery at D epartm ent of Breast and Thyroid Surgery of H unan Provincial People's H ospital from O ctober 2018 to February 2020. Using the HPLC-MS technology platform, multi-dimensional statistical analysis of differential metabolites in PTC tissues and adjacent tissues was performed to find abnormal metabolic pathways related to PTC. Results: PCA, PLS-DA, OPLS-DA analyses showed that the metabolic profiles of cancer tissues and adjacent tissues were significantly different. OPLS-Loading plot analysis screened 76 potential differential metabolites (VIP>1, FC>2, and P<0.05). Among them, 33 metabolites such as Leucyl-phenylalanine,2-Oxomelatonin and Vanillactic acid were up-regulated in PTC tissues; 43 metabolites such as 3-glucoside, glycerophospholipid,phosphatidylcholine and lactose were down-regulated in PTC tissues. 13 abnormal metabolic pathways related to differential metabolites that may be involved in the pathophysiological process of PTC metabolism were found, such as: cysteine and methionine metabolism, glycerophospholipid metabolism, pyrimidine metabolism, galactose metabolism and alanine, aspartic acid and glutamic acid metabolism, citric acid cycle and so on. There were five types of differential metabolites with an area under the ROC curve greater than 0.9, namely pimelic acid, solerol, suberic acid, Alpha-Lactose and L-Serine. Conclusion: The galactose metabolism and amino acid metabolism in PTC tissues have changed, and Warburg effect exists in cells of PTC tissues. Pimelic acid, solerol, suberic acid,Alpha-Lactose and L-Serine can be used to distinguish PTC from normal people.
Objective: To explore the metabolic differences between papillary thyroid carcinoma (PTC) tissues and adjacent tissues using tissue metabolomics methods, and to search for potential biomarkers of PTC as well as to explore the pathogenesis and treatment strategies for PTC. Methods: Collected cancer and para-cancerous tissue specim ens from 40 patients with PTC who had undergone breast surgery at D epartm ent of Breast and Thyroid Surgery of H unan Provincial People's H ospital from O ctober 2018 to February 2020. Using the HPLC-MS technology platform, multi-dimensional statistical analysis of differential metabolites in PTC tissues and adjacent tissues was performed to find abnormal metabolic pathways related to PTC. Results: PCA, PLS-DA, OPLS-DA analyses showed that the metabolic profiles of cancer tissues and adjacent tissues were significantly different. OPLS-Loading plot analysis screened 76 potential differential metabolites (VIP>1, FC>2, and P<0.05). Among them, 33 metabolites such as Leucyl-phenylalanine,2-Oxomelatonin and Vanillactic acid were up-regulated in PTC tissues; 43 metabolites such as 3-glucoside, glycerophospholipid,phosphatidylcholine and lactose were down-regulated in PTC tissues. 13 abnormal metabolic pathways related to differential metabolites that may be involved in the pathophysiological process of PTC metabolism were found, such as: cysteine and methionine metabolism, glycerophospholipid metabolism, pyrimidine metabolism, galactose metabolism and alanine, aspartic acid and glutamic acid metabolism, citric acid cycle and so on. There were five types of differential metabolites with an area under the ROC curve greater than 0.9, namely pimelic acid, solerol, suberic acid, Alpha-Lactose and L-Serine. Conclusion: The galactose metabolism and amino acid metabolism in PTC tissues have changed, and Warburg effect exists in cells of PTC tissues. Pimelic acid, solerol, suberic acid,Alpha-Lactose and L-Serine can be used to distinguish PTC from normal people.
PAN Junfan
,
WU Shiwen
,
TU Xunwei
,
XU Nengluan
,
LIN Ming
,
LIN Ying
,
XU Yiquan
,
WU Yun
,
LI Hongru
,
CHEN Yusheng
2020, 27(11):1272-1277.
DOI: 10.3872/j.issn.1007-385X.2020.11.010
Abstract:
Objective: To investigate the correlation between epidermal growth factor receptor (EGFR) gene mutation and prognosis of non-small cell lung cancer (NSCLC) with brain metastasis, so as to provide clinical basis for improving prognosis of NSCLC patients with brain metastasis and guiding individualized treatment. Methods: The clinical data of 88 patients with NSCLC complicated with brain metastasis admitted to Fujian Provincial Hospital from January 1, 2013 to September 30, 2018 were retrospectively analyzed.The time of death of the patients was obtained during follow-up, and the deadline of follow-up was October 31, 2019. Clinical data collected and analyzed include gender, age, smoking history, pathological type, gene detection, treatment, progression free survival (PFS), overall survival (OS), etc. Survival analysis (Kaplan-Meier survival time curve) was used to evaluate the prognosis of EGFR mutant patients. Single factor analysis (log-rank test) was used to predict the factors affecting the treatment efficacy of EGFR-TKIs.Results: 57 of 88 NSCLC patients with brain metastases were EGFR mutant. The median progression free survival (MPFS) of EGFR mutant patients was 13.0 months (95%CI: 11.951-14.049), which was significantly longer than that of EGFR wild type patients (P=0.003); and the median survival time (MST) of EGFR mutant patients was 29.0 months (95%CI: 20.531-37.468), which was also significantly longer than that of EGFR wild type patients (P=0.001). In EGFR mutant patients, the OS of patients with Exon19-del exon deletion was significantly longer than those with Exon21 L858R mutation (P=0.05). Compared with Exon21 L858R mutation group, the OS of patients in Exon19-del+Exon20T790M mutation group was prolonged (P=0.077). Conclusion: In NSCLC patients with brain metastasis, EGFR mutant patients has a better prognosis than wild-type patients, with the best prognosis in patients with single Exon19-deletion.
Objective: To investigate the correlation between epidermal growth factor receptor (EGFR) gene mutation and prognosis of non-small cell lung cancer (NSCLC) with brain metastasis, so as to provide clinical basis for improving prognosis of NSCLC patients with brain metastasis and guiding individualized treatment. Methods: The clinical data of 88 patients with NSCLC complicated with brain metastasis admitted to Fujian Provincial Hospital from January 1, 2013 to September 30, 2018 were retrospectively analyzed.The time of death of the patients was obtained during follow-up, and the deadline of follow-up was October 31, 2019. Clinical data collected and analyzed include gender, age, smoking history, pathological type, gene detection, treatment, progression free survival (PFS), overall survival (OS), etc. Survival analysis (Kaplan-Meier survival time curve) was used to evaluate the prognosis of EGFR mutant patients. Single factor analysis (log-rank test) was used to predict the factors affecting the treatment efficacy of EGFR-TKIs.Results: 57 of 88 NSCLC patients with brain metastases were EGFR mutant. The median progression free survival (MPFS) of EGFR mutant patients was 13.0 months (95%CI: 11.951-14.049), which was significantly longer than that of EGFR wild type patients (P=0.003); and the median survival time (MST) of EGFR mutant patients was 29.0 months (95%CI: 20.531-37.468), which was also significantly longer than that of EGFR wild type patients (P=0.001). In EGFR mutant patients, the OS of patients with Exon19-del exon deletion was significantly longer than those with Exon21 L858R mutation (P=0.05). Compared with Exon21 L858R mutation group, the OS of patients in Exon19-del+Exon20T790M mutation group was prolonged (P=0.077). Conclusion: In NSCLC patients with brain metastasis, EGFR mutant patients has a better prognosis than wild-type patients, with the best prognosis in patients with single Exon19-deletion.
2020, 27(11):1278-1283.
DOI: 10.3872/j.issn.1007-385X.2020.11.011
Abstract:
Objective: To screen differentially expressed genes (DEGs) and key pathways by analyzing the gene chip expression data of cisplatin sensitive and resistant strains of non-small cell lung cancer (NSCLC), and to explore the key cluster functions by constructing protein-protein interaction (PPI) networks. Methods：Gene chip expression data were obtained from GEO database, and the DEGs were screened by GEO2R tool; PPI network was constructed by STRING database and Cytoscape software, and relevant characteristic genes and signal pathway information were obtained by DAVID enrichment. Results：A total of 481 DEGs were obtained by microarray analysis. Compared with sensitive cell lines, 418 genes were up-regulated and 63 genes were down-regulated in cisplatin resistant cell lines. The DEGs were mainly enriched in piRNA metabolism, DNA methylation modification, cell mitosis and cell cycle progression etc. The protein complex was predicted to have 6 main functional clusters, which were respectively related to chemokine,keratinization, piRNA metabolism, cytokine receptor interaction, cytokine secretion regulation and chromatin silencing related biological processes. Conclusion：In this study, bioinformatics methods were used to find the characteristic genes and signaling pathways of cisplatin resistant cell lines, among which the significantly up-regulated genes such as SAA1, KRT5, TDRD9, BCL2A1,CSF1R and HIST1H1A and their functional groups may be the potential molecular mechanism of cisplatin resistance in NSCLC,providing a new theoretical basis for clinical precision therapy.
Objective: To screen differentially expressed genes (DEGs) and key pathways by analyzing the gene chip expression data of cisplatin sensitive and resistant strains of non-small cell lung cancer (NSCLC), and to explore the key cluster functions by constructing protein-protein interaction (PPI) networks. Methods：Gene chip expression data were obtained from GEO database, and the DEGs were screened by GEO2R tool; PPI network was constructed by STRING database and Cytoscape software, and relevant characteristic genes and signal pathway information were obtained by DAVID enrichment. Results：A total of 481 DEGs were obtained by microarray analysis. Compared with sensitive cell lines, 418 genes were up-regulated and 63 genes were down-regulated in cisplatin resistant cell lines. The DEGs were mainly enriched in piRNA metabolism, DNA methylation modification, cell mitosis and cell cycle progression etc. The protein complex was predicted to have 6 main functional clusters, which were respectively related to chemokine,keratinization, piRNA metabolism, cytokine receptor interaction, cytokine secretion regulation and chromatin silencing related biological processes. Conclusion：In this study, bioinformatics methods were used to find the characteristic genes and signaling pathways of cisplatin resistant cell lines, among which the significantly up-regulated genes such as SAA1, KRT5, TDRD9, BCL2A1,CSF1R and HIST1H1A and their functional groups may be the potential molecular mechanism of cisplatin resistance in NSCLC,providing a new theoretical basis for clinical precision therapy.
2020, 27(11):1284-1288.
DOI: 10.3872/j.issn.1007-385X.2020.11.012
Abstract:
环状 RAN（circular RAN，circRNA）是一种广泛存在于哺乳动物体内具有共价闭合环状结构的非编码 RAN。CircRNA具有高度的稳定性和保守性，成为近年来表观遗传学领域研究的热点。肿瘤转移是导致肿瘤患者死亡最主要的原因，提高对肿瘤转移机制的理解至关重要。随着对 circRNA 研究的逐渐深入，其在肿瘤转移中的作用及相关机制逐渐被挖掘。CircRNA通过影响上皮间质转化（epithelial-mesenchymal transition，EMT）、肿瘤免疫逃逸、肿瘤血管生成、DNA甲基化修饰和外泌体功能等方面在肿瘤转移中发挥重要作用，为肿瘤转移的机制研究提供了新的思路。因此，circRNA有望成为新的肿瘤标志物和治疗靶点。本文就circRNA的结构特征及其在肿瘤转移中的作用作一综述。
环状 RAN（circular RAN，circRNA）是一种广泛存在于哺乳动物体内具有共价闭合环状结构的非编码 RAN。CircRNA具有高度的稳定性和保守性，成为近年来表观遗传学领域研究的热点。肿瘤转移是导致肿瘤患者死亡最主要的原因，提高对肿瘤转移机制的理解至关重要。随着对 circRNA 研究的逐渐深入，其在肿瘤转移中的作用及相关机制逐渐被挖掘。CircRNA通过影响上皮间质转化（epithelial-mesenchymal transition，EMT）、肿瘤免疫逃逸、肿瘤血管生成、DNA甲基化修饰和外泌体功能等方面在肿瘤转移中发挥重要作用，为肿瘤转移的机制研究提供了新的思路。因此，circRNA有望成为新的肿瘤标志物和治疗靶点。本文就circRNA的结构特征及其在肿瘤转移中的作用作一综述。
2020, 27(11):1289-1294.
DOI: 10.3872/j.issn.1007-385X.2020.11.013
Abstract:
长链非编码RNA（lncRNA）是一类转录本长度超过200个核苷酸的小分子RNA，不具有蛋白编码功能，起初被认为是基因组转录的“噪音”，近年来却被证实在生物体内对基因的表达具有调控作用，与肿瘤的发生发展密切相关。肺癌是一种严重危害人们健康的恶性肿瘤性疾病，研究发现lncRNA在肺肿瘤中表达失调，异常表达的lncRNA能作为关键的调控因子，参与多种生物学过程，影响肿瘤转移与侵袭、肺癌细胞的增殖和凋亡、肿瘤血管生成及调节肿瘤耐药，为肺癌临床治疗提供新思路。此外，lncRNA还可作为潜在的生物标志物用于肺癌早期诊断及评估肺癌预后。本文就lncRNA在肺癌研究中的进展进行综述。
长链非编码RNA（lncRNA）是一类转录本长度超过200个核苷酸的小分子RNA，不具有蛋白编码功能，起初被认为是基因组转录的“噪音”，近年来却被证实在生物体内对基因的表达具有调控作用，与肿瘤的发生发展密切相关。肺癌是一种严重危害人们健康的恶性肿瘤性疾病，研究发现lncRNA在肺肿瘤中表达失调，异常表达的lncRNA能作为关键的调控因子，参与多种生物学过程，影响肿瘤转移与侵袭、肺癌细胞的增殖和凋亡、肿瘤血管生成及调节肿瘤耐药，为肺癌临床治疗提供新思路。此外，lncRNA还可作为潜在的生物标志物用于肺癌早期诊断及评估肺癌预后。本文就lncRNA在肺癌研究中的进展进行综述。
2020, 27(11):1295-1298.
DOI: 10.3872/j.issn.1007-385X.2020.11.014
Abstract:
活性氧（reactive oxygen species，ROS）是癌症细胞信号转导机制中不可或缺的一环。ROS含量的多少将决定它所产生的生物学效应。高含量的ROS可能会引起组织损坏和细胞死亡，低水平的ROS可能具有增殖作用。ROS不仅能够在非小细胞肺癌（non-small cell lung cancer，NSCLC）的肿瘤细胞内产生，也是肿瘤生长环境的重要组成部分。本文从ROS的生物学特性及其细胞免疫机制角度出发，阐述不同含量的ROS通过参与多种的信号通路改变肿瘤微环境（tumor microenvironment，TME），从而发挥调节PD-1/PD-L1免疫抑制作用，对Treg、MDSC以及TAM生物活性的影响等，对ROS在NSCLC肿瘤免疫的研究进展进行综述。
活性氧（reactive oxygen species，ROS）是癌症细胞信号转导机制中不可或缺的一环。ROS含量的多少将决定它所产生的生物学效应。高含量的ROS可能会引起组织损坏和细胞死亡，低水平的ROS可能具有增殖作用。ROS不仅能够在非小细胞肺癌（non-small cell lung cancer，NSCLC）的肿瘤细胞内产生，也是肿瘤生长环境的重要组成部分。本文从ROS的生物学特性及其细胞免疫机制角度出发，阐述不同含量的ROS通过参与多种的信号通路改变肿瘤微环境（tumor microenvironment，TME），从而发挥调节PD-1/PD-L1免疫抑制作用，对Treg、MDSC以及TAM生物活性的影响等，对ROS在NSCLC肿瘤免疫的研究进展进行综述。
2020, 27(11):1299-1303.
DOI: 10.3872/j.issn.1007-385X.2020.11.015
Abstract:
食管鳞癌（esophageal squamous cell carcinoma, ESCC）是世界上发病率和致死率较高的肿瘤之一，近79%的ESCC发生在亚洲国家。近年来，几项大规模研究应用二代测序(next-generation sequencing, NGS)技术确定了ESCC的体细胞突变图谱，并进一步解析常见的突变特征及与吸烟、饮酒、预后等相关的突变特征，识别潜在的驱动基因，分析拷贝数变异（copy number variation, CNV）,富集分析基于基因组数据的信号通路，为精准靶向治疗和精准免疫治疗提供了理论基础，有助于了解ESCC的分子机制和发生发展过程。本文总结了近期在ESCC基因组学领域取得的研究进展，尤其是研究中发现新的治疗靶标以及诊断和预后的生物标志物，为制定更加精准的治疗方案提供了可能。
食管鳞癌（esophageal squamous cell carcinoma, ESCC）是世界上发病率和致死率较高的肿瘤之一，近79%的ESCC发生在亚洲国家。近年来，几项大规模研究应用二代测序(next-generation sequencing, NGS)技术确定了ESCC的体细胞突变图谱，并进一步解析常见的突变特征及与吸烟、饮酒、预后等相关的突变特征，识别潜在的驱动基因，分析拷贝数变异（copy number variation, CNV）,富集分析基于基因组数据的信号通路，为精准靶向治疗和精准免疫治疗提供了理论基础，有助于了解ESCC的分子机制和发生发展过程。本文总结了近期在ESCC基因组学领域取得的研究进展，尤其是研究中发现新的治疗靶标以及诊断和预后的生物标志物，为制定更加精准的治疗方案提供了可能。
2020, 27(11):1304-1308.
DOI: 10.3872/j.issn.1007-385X.2020.11.016
Abstract:
卵巢癌死亡率自90年代以来始终高居妇科恶性肿瘤之首，对化疗药物耐药是导致大多数患者复发的根本原因。卵巢癌易感性及化疗敏感性等在不同患者间具有个体差异，广泛构成了人类基因组所有变异的单核苷酸多态性（single nucleotide polymorphism，SNP）可能是解释此种差异的原因之一。在近年的报道中，从SNP角度进行卵巢癌分子机制的研究越来越多，为肿瘤的遗传性、发生发展和治疗提供了新的思路，并且有潜力作为重要的基因工具应用于生物医学各个领域中。本文就近5年来PubMed上收录发表的卵巢癌易感性、化学治疗以及预后相关的SNP研究作一综述。
卵巢癌死亡率自90年代以来始终高居妇科恶性肿瘤之首，对化疗药物耐药是导致大多数患者复发的根本原因。卵巢癌易感性及化疗敏感性等在不同患者间具有个体差异，广泛构成了人类基因组所有变异的单核苷酸多态性（single nucleotide polymorphism，SNP）可能是解释此种差异的原因之一。在近年的报道中，从SNP角度进行卵巢癌分子机制的研究越来越多，为肿瘤的遗传性、发生发展和治疗提供了新的思路，并且有潜力作为重要的基因工具应用于生物医学各个领域中。本文就近5年来PubMed上收录发表的卵巢癌易感性、化学治疗以及预后相关的SNP研究作一综述。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.