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Volume 32,Issue 5,2025 Table of Contents
2025, 32(5):453-459.
Abstract:
[Abstract] Chimeric antigen receptor gene-modified T lymphocytes (CAR-T cells) have made significant progress in the treatment of hematologic malignancies. However, the uncertainties and lack of controllability associated with their in vivo behavior remain major limitations to their clinical application. Uncontrolled or inappropriate activation of CAR-T cells at unintended locations can lead to reduced antitumor efficacy or unpredictable adverse reactions. Enabling CAR-T cells to exhibit predictable and controllable behavior in vivo, with activation occurring at the right location and at the appropriate intensity, holds the potential to significantly enhance their antitumor effectiveness and minimize adverse effects. This article systematically reviews recent strategies for "remotely controlling" CAR-T cell activity in vivo through innovative designs that allow precise regulation of CAR-T cell activity and behavior. Achieving safe, targeted, and efficient antitumor responses represents one of the key directions for the future development of CAR-T cell therapies.
[Abstract] Chimeric antigen receptor gene-modified T lymphocytes (CAR-T cells) have made significant progress in the treatment of hematologic malignancies. However, the uncertainties and lack of controllability associated with their in vivo behavior remain major limitations to their clinical application. Uncontrolled or inappropriate activation of CAR-T cells at unintended locations can lead to reduced antitumor efficacy or unpredictable adverse reactions. Enabling CAR-T cells to exhibit predictable and controllable behavior in vivo, with activation occurring at the right location and at the appropriate intensity, holds the potential to significantly enhance their antitumor effectiveness and minimize adverse effects. This article systematically reviews recent strategies for "remotely controlling" CAR-T cell activity in vivo through innovative designs that allow precise regulation of CAR-T cell activity and behavior. Achieving safe, targeted, and efficient antitumor responses represents one of the key directions for the future development of CAR-T cell therapies.
2025, 32(5):460-468.
Abstract:
[Abstract] Objective: To explore the role of circ_0007766 molecule cyclized from the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene in prostate cancer (PCa) cells and the impact of hypoxia on the regulation of its expression. Methods: The expression of circ_0007766 molecule in PCa cells and tissues was detected by qRT-PCR. The siRNA of circ0007766 was transfected to PCa cells (DU145 cell and PC3 cell) respectively; Colony formation assay, CCK-8 assay and Transwell assay were performed to detect the effect of circ_0007766 knockdown on the colony formation, proliferation, migration, and invasion abilities of PCa cells. Hypoxia cell model of DU145 and PC3 cells were established by hypoxic chamber method, and WB was performed to detect the protein expression of HIF-1α, a key molecule of the hypoxic pathway. qRT-PCR was performed to detect the expression of circ_0007766 molecule in hypoxic cell model, and the protein expression of RNA-binding protein eukaryotic translation initiation factor 4A3 (EIF4A3) was detected by WB. RNA immunoprecipitation (RIP) was performed to detect the binding of EIF4A3 to circ_0007766 under hypoxic conditions. qRT-PCR assay was performed to further detect the effect of EIF4A3 knockdown on the expression of circ_0007766 under hypoxic conditions. Results: circ_0007766 was highly expressed in PCa cells (P < 0.01) and PCa tissues (P < 0.05). The knockdown of circ_0007766 (P < 0.05 or P < 0.01) could significantly inhibit the proliferation, migration and invasion abilities of PCa cells (all P < 0.01). The upregulation of HIF-1α protein under hypoxic conditions confirmed the successful establishment of the hypoxia cell model. qRT-PCR analysis revealed that compared with that in the normoxia group, circ_0007766 expression was markedly elevated in the hypoxia group (P < 0.01). WB analysis demonstrated increased EIF4A3 protein expression in cells of the hypoxia group. RIP assays indicated that circ_0007766 was highly concentrated in the EIF4A3-enriched group (P <0.01). Additionally, qRT-PCR showed that hypoxia significantly boosted circ_0007766 expression, whereas EIF4A3 knockdown notably diminished the hypoxia-induced expression of circ_0007766 (P < 0.05 or P < 0.01). Conclusion: Circ-0007766 plays the role of cancer-promoting molecule in PCa cells, and its expression is related to the regulation of EIF4A3 molecule under hypoxic conditions.
[Abstract] Objective: To explore the role of circ_0007766 molecule cyclized from the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene in prostate cancer (PCa) cells and the impact of hypoxia on the regulation of its expression. Methods: The expression of circ_0007766 molecule in PCa cells and tissues was detected by qRT-PCR. The siRNA of circ0007766 was transfected to PCa cells (DU145 cell and PC3 cell) respectively; Colony formation assay, CCK-8 assay and Transwell assay were performed to detect the effect of circ_0007766 knockdown on the colony formation, proliferation, migration, and invasion abilities of PCa cells. Hypoxia cell model of DU145 and PC3 cells were established by hypoxic chamber method, and WB was performed to detect the protein expression of HIF-1α, a key molecule of the hypoxic pathway. qRT-PCR was performed to detect the expression of circ_0007766 molecule in hypoxic cell model, and the protein expression of RNA-binding protein eukaryotic translation initiation factor 4A3 (EIF4A3) was detected by WB. RNA immunoprecipitation (RIP) was performed to detect the binding of EIF4A3 to circ_0007766 under hypoxic conditions. qRT-PCR assay was performed to further detect the effect of EIF4A3 knockdown on the expression of circ_0007766 under hypoxic conditions. Results: circ_0007766 was highly expressed in PCa cells (P < 0.01) and PCa tissues (P < 0.05). The knockdown of circ_0007766 (P < 0.05 or P < 0.01) could significantly inhibit the proliferation, migration and invasion abilities of PCa cells (all P < 0.01). The upregulation of HIF-1α protein under hypoxic conditions confirmed the successful establishment of the hypoxia cell model. qRT-PCR analysis revealed that compared with that in the normoxia group, circ_0007766 expression was markedly elevated in the hypoxia group (P < 0.01). WB analysis demonstrated increased EIF4A3 protein expression in cells of the hypoxia group. RIP assays indicated that circ_0007766 was highly concentrated in the EIF4A3-enriched group (P <0.01). Additionally, qRT-PCR showed that hypoxia significantly boosted circ_0007766 expression, whereas EIF4A3 knockdown notably diminished the hypoxia-induced expression of circ_0007766 (P < 0.05 or P < 0.01). Conclusion: Circ-0007766 plays the role of cancer-promoting molecule in PCa cells, and its expression is related to the regulation of EIF4A3 molecule under hypoxic conditions.
2025, 32(5):469-475.
Abstract:
[Abstract] Objective: To explore the effect of β-galactoside α-2-6sialyltransferase1 (ST6GAL1) on glycolysis, migration and invasion of colorectal cancer (CRC) HCT116 cells and its possible molecular mechanisms. Methods: The difference in the expression of ST6GAL1 in CRC patients and healthy people was analyzed using the GEPIA2 database. WB was performed to detect the differences in the expressions of ST6GAL1 in CRC cell lines HCT116, SW480, Caco-2, HT29, LoVo and human normal colon epithelial cell line NCM460. The difference in the expressions of ST6GAL1 in CRC tissues and corresponding adjacent tissues was analyzed by immunohistochemistry. HCT116 cell lines with stably knocked down or overexpressed ST6GAL1 were constructed by lentivirus transfection. Cell migration ability was detected by scratch test. Cell invasion ability was detected by Transwell test. WB assay was performed to detect the expression levels of cell glycolysis related proteins and Notch1 intracellular domain (Notch1 ICD) as well as the phosphorylation level of PI3K/AKT/mTOR pathway. The expression level of Notch1 ICD and its entry into nucleus were observed by immunofluorescence assay. The Notch1 receptor agonist Jagged1 was added to HCT116 cells, and the expression levels of glycolysis-related proteins and Notch1 ICD and PI3K/AKT/mTOR pathway phosphorylation level were detected by WB. Results: The expression of ST6GAL1 was up-regulated in CRC tissues and cells (all P < 0.05). Compared with the control and overexpression groups, knockdown of ST6GAL1 resulted in significantly lower levels of Notch1 ICD expression and PI3K/AKT/mTORC1 phosphorylation in HCT116 cells, lower levels of cellular glycolysis-related protein expressions and weaker cell migration and invasion abilities (all P < 0.05). Overexpression of ST6GAL1 increased Notch1 ICD expression levels within HCT116 cells and promoted their entry into the nucleus. Cell glycolysis-related protein expression levels were elevated (all P < 0.05). Cell migration and invasion abilities were enhanced (all P < 0.05). Conclusion: ST6GAL1 activates the PI3K/AKT/mTORC1 pathway through activation of Notch1 receptor and phosphorylation, thus enhancing the glycolytic level and migration and invasion abilities of CRC cells.
[Abstract] Objective: To explore the effect of β-galactoside α-2-6sialyltransferase1 (ST6GAL1) on glycolysis, migration and invasion of colorectal cancer (CRC) HCT116 cells and its possible molecular mechanisms. Methods: The difference in the expression of ST6GAL1 in CRC patients and healthy people was analyzed using the GEPIA2 database. WB was performed to detect the differences in the expressions of ST6GAL1 in CRC cell lines HCT116, SW480, Caco-2, HT29, LoVo and human normal colon epithelial cell line NCM460. The difference in the expressions of ST6GAL1 in CRC tissues and corresponding adjacent tissues was analyzed by immunohistochemistry. HCT116 cell lines with stably knocked down or overexpressed ST6GAL1 were constructed by lentivirus transfection. Cell migration ability was detected by scratch test. Cell invasion ability was detected by Transwell test. WB assay was performed to detect the expression levels of cell glycolysis related proteins and Notch1 intracellular domain (Notch1 ICD) as well as the phosphorylation level of PI3K/AKT/mTOR pathway. The expression level of Notch1 ICD and its entry into nucleus were observed by immunofluorescence assay. The Notch1 receptor agonist Jagged1 was added to HCT116 cells, and the expression levels of glycolysis-related proteins and Notch1 ICD and PI3K/AKT/mTOR pathway phosphorylation level were detected by WB. Results: The expression of ST6GAL1 was up-regulated in CRC tissues and cells (all P < 0.05). Compared with the control and overexpression groups, knockdown of ST6GAL1 resulted in significantly lower levels of Notch1 ICD expression and PI3K/AKT/mTORC1 phosphorylation in HCT116 cells, lower levels of cellular glycolysis-related protein expressions and weaker cell migration and invasion abilities (all P < 0.05). Overexpression of ST6GAL1 increased Notch1 ICD expression levels within HCT116 cells and promoted their entry into the nucleus. Cell glycolysis-related protein expression levels were elevated (all P < 0.05). Cell migration and invasion abilities were enhanced (all P < 0.05). Conclusion: ST6GAL1 activates the PI3K/AKT/mTORC1 pathway through activation of Notch1 receptor and phosphorylation, thus enhancing the glycolytic level and migration and invasion abilities of CRC cells.
2025, 32(5):476-483.
Abstract:
[Abstract] Objective: To investigate the effect of long non-coding RNA glucuronidase β pseudogene 11 (GUSBP11) regulating miR-339-5p/mouse two-minute homolog 2 (MDM2) axis on the proliferation, migration, and invasion of gastric cancer AGS cells. Methods: Cancerous and adjacent tissues from 25 gastric cancer patients who underwent surgical treatment at Foshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from December 2023 to June 2024 were collected. Gastric cancer AGS cells and normal gastric mucosal epithelial GES-1 cells were routinely cultured. The control plasmids and knockdown plasmids were transfected into AGS cells using transfection reagents, dividing the cells into Ctrl group, sh-NC group, sh-GUSBP11 group, sh-GUSBP11 + anti-NC group, and sh-GUSBP11 + anti-miR-339-5p group. The mRNA expression of GUSBP11, miR-339-5p, and MDM2 in gastric cancer tissues and cells of each group was detected by qPCR. A dual-luciferase reporter gene assay was used to detect the targeting relationship between GUSBP11 or MDM2 and miR-339-5p. EdU staining, scratch healing assay, and Transwell chamber assay were adopted to assess the proliferation, migration, and invasion abilities of AGS cells, respectively. WB assay was used to measure the protein expression of CDK1, MMP-2, and MMP-9 in AGC cells. The effects of GUSBP11 knockdown on tumor growth were examined through AGS cell xenograft experiments. Results: The mRNA expression of GUSBP11 and MDM2 were significantly upregulated in gastric cancer tissues and cells (both P < 0.05), while miR-339-5p was significantly downregulated (P < 0.05). A targeting relationship was found between GUSBP11 and miR-339-5p, as well as between MDM2 and miR-339-5p. Knockdown of GUSBP11 in AGS cells significantly inhibited MDM2 protein expression and promoted miR-339-5p expression, while inhibition of miR-339-5p promoted MDM2 protein expression. GUSBP11 knockdown significantly inhibited the proliferation, migration, and invasion of AGS cells, while inhibition of miR-339-5p reversed this effect. GUSBP11 knockdown significantly inhibited the protein expression of CDK1, MMP-2, and MMP-9, and inhibition of miR-339-5p reversed this effect. Furthermore, GUSBP11 knockdown significantly inhibited the growth of AGS cell xenografts. Conclusion: GUSBP11 is highly expressed in gastric cancer tissues and cells, and knocking down GUSBP11 expression may inhibit malignant biological behaviors of gastric cancer cells through regulating the miR-339-5p/DM2 axis.
[Abstract] Objective: To investigate the effect of long non-coding RNA glucuronidase β pseudogene 11 (GUSBP11) regulating miR-339-5p/mouse two-minute homolog 2 (MDM2) axis on the proliferation, migration, and invasion of gastric cancer AGS cells. Methods: Cancerous and adjacent tissues from 25 gastric cancer patients who underwent surgical treatment at Foshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from December 2023 to June 2024 were collected. Gastric cancer AGS cells and normal gastric mucosal epithelial GES-1 cells were routinely cultured. The control plasmids and knockdown plasmids were transfected into AGS cells using transfection reagents, dividing the cells into Ctrl group, sh-NC group, sh-GUSBP11 group, sh-GUSBP11 + anti-NC group, and sh-GUSBP11 + anti-miR-339-5p group. The mRNA expression of GUSBP11, miR-339-5p, and MDM2 in gastric cancer tissues and cells of each group was detected by qPCR. A dual-luciferase reporter gene assay was used to detect the targeting relationship between GUSBP11 or MDM2 and miR-339-5p. EdU staining, scratch healing assay, and Transwell chamber assay were adopted to assess the proliferation, migration, and invasion abilities of AGS cells, respectively. WB assay was used to measure the protein expression of CDK1, MMP-2, and MMP-9 in AGC cells. The effects of GUSBP11 knockdown on tumor growth were examined through AGS cell xenograft experiments. Results: The mRNA expression of GUSBP11 and MDM2 were significantly upregulated in gastric cancer tissues and cells (both P < 0.05), while miR-339-5p was significantly downregulated (P < 0.05). A targeting relationship was found between GUSBP11 and miR-339-5p, as well as between MDM2 and miR-339-5p. Knockdown of GUSBP11 in AGS cells significantly inhibited MDM2 protein expression and promoted miR-339-5p expression, while inhibition of miR-339-5p promoted MDM2 protein expression. GUSBP11 knockdown significantly inhibited the proliferation, migration, and invasion of AGS cells, while inhibition of miR-339-5p reversed this effect. GUSBP11 knockdown significantly inhibited the protein expression of CDK1, MMP-2, and MMP-9, and inhibition of miR-339-5p reversed this effect. Furthermore, GUSBP11 knockdown significantly inhibited the growth of AGS cell xenografts. Conclusion: GUSBP11 is highly expressed in gastric cancer tissues and cells, and knocking down GUSBP11 expression may inhibit malignant biological behaviors of gastric cancer cells through regulating the miR-339-5p/DM2 axis.
2025, 32(5):484-491.
Abstract:
[Abstract] Objective: To investigate the effects of long non-coding RNA 01694 (LINC01694) regulating the microRNA-128-3p (miR-128-3p)/telomeric repeat binding factor 1 (TERF1) axis on the malignant biological behaviors of prostate cancer (PC) cells. Methods: Cancer tissues and corresponding adjacent tissues from 20 PC patients undergoing surgery at the Department of Urology, Jingzhou Central Hospital, between January 2023 and January 2024 were collected. Human PC cell lines (PC-3, DU145, LNCaP, C4-2) and normal human prostate epithelial RWPE-1 cells were routinely cultured. LNCaP cells were transfected with sh-LINC01694, sh-NC, miR-128-3p inhibitor, inhibitor-NC, miR-128-3pmimics, pcDNA, and pcDNA-LINC01694 using Lipo6000? transfection reagent. Cells were divided into the following groups: Ctrl, sh-NC, sh-LINC01694, sh-LINC01694 + NC inhibitor, sh-LINC01694 + miR-128-3p inhibitor, pcDNA, and pcDNA LINC01694 groups. The mRNA expression of LINC01694, miR-128-3p, and TERF1 in PC tissues and cells, as well as LNCap cells in each group, was detected by qPCR. The protein expression of TERF1, caspase-3, cyclin D1, E-cadherin, and N-cadherin in LNCaP cells of each group was detected by WB method. Clone formation assay, flow cytometry, and Transwell chamber assay were applied to detect proliferation, apoptosis, migration, and invasion of LNCaP cells, respectively. Dual luciferase reporter gene assay, RNA pull-down assay, and RNA-binding protein immunoprecipitation (RIP) assay were applied to verify the targeting binding relationship between LINC01694 and miR-128-3p as well as between TERF1 and miR-128-3p. Nude mouse LNCaP cell xenograft experiment was conducted to assess the effect of LINC01694 knockdown on tumor growth. Results: LINC01694 was highly expressed in PC tissues and cells (all P<0.05). Knockdown of LINC01694 in LNCaP cells promoted the protein expression of miR-128-3p, caspase-3, and E-cadherin, inhibited the protein expression of LINC01694, TERF1, cyclin D1, and N-cadherin, reduced cell proliferation, migration, and invasion, and promoted apoptosis (all P < 0.05). All these effects were partially reversed by the miR 128-3p inhibitor (all P < 0.05). LINC01694 could directly bind to miR-128-3p (P < 0.05), while miR-128-3p could directly bind to TERF1 mRNA (P < 0.05), indicating that LINC01694 regulates the miR-128-3p/TERF1 axis. Knockdown of LINC01694 significantly inhibited the growth of LNCaP cell xenografts in nude mice (P < 0.05). Conclusion: LINC01694 regulates the malignant biological behaviors of LNCaP cells through the miR-128-3p/TERF1 axis.
[Abstract] Objective: To investigate the effects of long non-coding RNA 01694 (LINC01694) regulating the microRNA-128-3p (miR-128-3p)/telomeric repeat binding factor 1 (TERF1) axis on the malignant biological behaviors of prostate cancer (PC) cells. Methods: Cancer tissues and corresponding adjacent tissues from 20 PC patients undergoing surgery at the Department of Urology, Jingzhou Central Hospital, between January 2023 and January 2024 were collected. Human PC cell lines (PC-3, DU145, LNCaP, C4-2) and normal human prostate epithelial RWPE-1 cells were routinely cultured. LNCaP cells were transfected with sh-LINC01694, sh-NC, miR-128-3p inhibitor, inhibitor-NC, miR-128-3pmimics, pcDNA, and pcDNA-LINC01694 using Lipo6000? transfection reagent. Cells were divided into the following groups: Ctrl, sh-NC, sh-LINC01694, sh-LINC01694 + NC inhibitor, sh-LINC01694 + miR-128-3p inhibitor, pcDNA, and pcDNA LINC01694 groups. The mRNA expression of LINC01694, miR-128-3p, and TERF1 in PC tissues and cells, as well as LNCap cells in each group, was detected by qPCR. The protein expression of TERF1, caspase-3, cyclin D1, E-cadherin, and N-cadherin in LNCaP cells of each group was detected by WB method. Clone formation assay, flow cytometry, and Transwell chamber assay were applied to detect proliferation, apoptosis, migration, and invasion of LNCaP cells, respectively. Dual luciferase reporter gene assay, RNA pull-down assay, and RNA-binding protein immunoprecipitation (RIP) assay were applied to verify the targeting binding relationship between LINC01694 and miR-128-3p as well as between TERF1 and miR-128-3p. Nude mouse LNCaP cell xenograft experiment was conducted to assess the effect of LINC01694 knockdown on tumor growth. Results: LINC01694 was highly expressed in PC tissues and cells (all P<0.05). Knockdown of LINC01694 in LNCaP cells promoted the protein expression of miR-128-3p, caspase-3, and E-cadherin, inhibited the protein expression of LINC01694, TERF1, cyclin D1, and N-cadherin, reduced cell proliferation, migration, and invasion, and promoted apoptosis (all P < 0.05). All these effects were partially reversed by the miR 128-3p inhibitor (all P < 0.05). LINC01694 could directly bind to miR-128-3p (P < 0.05), while miR-128-3p could directly bind to TERF1 mRNA (P < 0.05), indicating that LINC01694 regulates the miR-128-3p/TERF1 axis. Knockdown of LINC01694 significantly inhibited the growth of LNCaP cell xenografts in nude mice (P < 0.05). Conclusion: LINC01694 regulates the malignant biological behaviors of LNCaP cells through the miR-128-3p/TERF1 axis.
2025, 32(5):492-497.
Abstract:
[Abstract] Objective: To compare the performance differences of domestic and imported CD3/CD28 activation beads for manufacturing CAR-T cells, providing a backup or alternative for domestic CAR-T cell research and manufacture. Methods: A mature protocol using imported CD3/CD28 activation beads with a 1∶1 ratio for CD3+ T cells was implemented as research control. Domestic beads were used with gradient ratios of 1∶2, 1∶1, and 2∶1 to activate T cells. 72 h after T cell activation, CAR-T cells were manufactured by CAR lentiviral infection and cell proliferation was monitored at 2-, 4-, and 7-days post-infection. Flow Cytometry was used to detect CAR-T cell positivity 5 days after infection and to detectCD4/CD8 phenotype of CAR-T cells and PD1+ TIM3+ cell exhaustion ratio 8 days after infection. Results: CAR-T cells manufactured by domestic CD3/CD28 activation beads exhibited similar phenotype compared with those manufactured by imported CD4/CD8 beads. The positive rate of CAR-T cells prepared with domestic beads was slightly lower than that of imported beads (53.7% vs 57.9%). However, the proliferation of CAR-T cells manufactured by domestic beads was about twice that of cells manufactured by imported beads, and the exhaustion level was only half that of imported beads (4.21% vs 7.91%). Moreover, the use of domestic magnetic beads was lower than that of imported magnetic beads, which was advantageous for cutting the costs of CAR-T cells research and manufacture. Conclusion: Domestic CD3/CD28 activation beads used for CAR-T cells manufacturing demonstrate comparable overall performance to their imported counterparts, showing potential as a backup or alternative for imported beads.
[Abstract] Objective: To compare the performance differences of domestic and imported CD3/CD28 activation beads for manufacturing CAR-T cells, providing a backup or alternative for domestic CAR-T cell research and manufacture. Methods: A mature protocol using imported CD3/CD28 activation beads with a 1∶1 ratio for CD3+ T cells was implemented as research control. Domestic beads were used with gradient ratios of 1∶2, 1∶1, and 2∶1 to activate T cells. 72 h after T cell activation, CAR-T cells were manufactured by CAR lentiviral infection and cell proliferation was monitored at 2-, 4-, and 7-days post-infection. Flow Cytometry was used to detect CAR-T cell positivity 5 days after infection and to detectCD4/CD8 phenotype of CAR-T cells and PD1+ TIM3+ cell exhaustion ratio 8 days after infection. Results: CAR-T cells manufactured by domestic CD3/CD28 activation beads exhibited similar phenotype compared with those manufactured by imported CD4/CD8 beads. The positive rate of CAR-T cells prepared with domestic beads was slightly lower than that of imported beads (53.7% vs 57.9%). However, the proliferation of CAR-T cells manufactured by domestic beads was about twice that of cells manufactured by imported beads, and the exhaustion level was only half that of imported beads (4.21% vs 7.91%). Moreover, the use of domestic magnetic beads was lower than that of imported magnetic beads, which was advantageous for cutting the costs of CAR-T cells research and manufacture. Conclusion: Domestic CD3/CD28 activation beads used for CAR-T cells manufacturing demonstrate comparable overall performance to their imported counterparts, showing potential as a backup or alternative for imported beads.
2025, 32(5):498-509.
Abstract:
[Abstract] Objective: To analyze by bioinformatics the association between the expression of membrane-associated tyrosine/threonine protein kinase 1 (PKMYT1) in glioma with its prognostic value, biological function, drug sensitivity, gene mutation, and immune infiltration. Methods: The differential expression of PKMYT1 was analyzed based on the Chinese Glioma Genome Atlas database (CGGA) and the Cancer Genome Atlas database (TCGA). Pathways likely to be enriched for PKMYT1 were predicted by gene ontology analysis (GO) and gene set enrichment analysis (GSEA). PKMYT1 was subjected to Pearson correlation and gene set variation analysis (GSVA) with cell cycle-related genes and gene sets. The survival prognosis, gene mutation, drug sensitivity and immune infiltration were further analyzed for PKMYT1 high and low expression groups of glioma patients. Results: PKMYT1 was significantly highly expressed in WHO high-grade glioma (P < 0.000 1), IDH wild-type glioma (P < 0.05), and glioblastoma (P < 0.000 1). Overall survival (OS) of patients in the PKMYT1 low expression group was significantly higher than that of the high expression group (P < 0.05). Cox regression analysis showed that PKMYT1 expression level was an independent prognostic factor for OS (P < 0.05). GO and GSEA analyses showed that the gene sets co-expressed with PKMYT1 were mainly enriched in signaling pathways such as cell cycle, DNA replication and DNA damage repair. Pearson correlation and GSVA analyses showed that the expression of PKMYT1 was significantly and positively correlated with the cell cycle-related genes, gene sets and cell cycle checkpoint genes (P < 0.01). Drug sensitivity analysis revealed that patients in the PKMYT1 high expression group had high sensitivity osimertinib, dabrafenib, carmustine and cediranib (P < 0.05). Mutation analysis revealed that the IDH1 gene had a higher mutation frequency in the PKMYT1 low expression group. The results of immune infiltration analysis showed that PKMYT1 expression was significantly positively correlated with glioma stroma score (r = 0.13, P < 0.001), immune score (r = 0.11, P < 0.01) and ESTIMATE score (r = 0.13, P < 0.001); and was significantly positively correlated with immune cell infiltration level of regulatory T (Treg) cells and M2-type macrophages (P < 0.05). Conclusion: Patients with high PKMYT1 expression have a poorer prognosis, and the mechanism may be related to tumor immune infiltration and cell cycle regulation. PKMYT1 is expected to be a potential target for the diagnosis and treatment of glioma.
[Abstract] Objective: To analyze by bioinformatics the association between the expression of membrane-associated tyrosine/threonine protein kinase 1 (PKMYT1) in glioma with its prognostic value, biological function, drug sensitivity, gene mutation, and immune infiltration. Methods: The differential expression of PKMYT1 was analyzed based on the Chinese Glioma Genome Atlas database (CGGA) and the Cancer Genome Atlas database (TCGA). Pathways likely to be enriched for PKMYT1 were predicted by gene ontology analysis (GO) and gene set enrichment analysis (GSEA). PKMYT1 was subjected to Pearson correlation and gene set variation analysis (GSVA) with cell cycle-related genes and gene sets. The survival prognosis, gene mutation, drug sensitivity and immune infiltration were further analyzed for PKMYT1 high and low expression groups of glioma patients. Results: PKMYT1 was significantly highly expressed in WHO high-grade glioma (P < 0.000 1), IDH wild-type glioma (P < 0.05), and glioblastoma (P < 0.000 1). Overall survival (OS) of patients in the PKMYT1 low expression group was significantly higher than that of the high expression group (P < 0.05). Cox regression analysis showed that PKMYT1 expression level was an independent prognostic factor for OS (P < 0.05). GO and GSEA analyses showed that the gene sets co-expressed with PKMYT1 were mainly enriched in signaling pathways such as cell cycle, DNA replication and DNA damage repair. Pearson correlation and GSVA analyses showed that the expression of PKMYT1 was significantly and positively correlated with the cell cycle-related genes, gene sets and cell cycle checkpoint genes (P < 0.01). Drug sensitivity analysis revealed that patients in the PKMYT1 high expression group had high sensitivity osimertinib, dabrafenib, carmustine and cediranib (P < 0.05). Mutation analysis revealed that the IDH1 gene had a higher mutation frequency in the PKMYT1 low expression group. The results of immune infiltration analysis showed that PKMYT1 expression was significantly positively correlated with glioma stroma score (r = 0.13, P < 0.001), immune score (r = 0.11, P < 0.01) and ESTIMATE score (r = 0.13, P < 0.001); and was significantly positively correlated with immune cell infiltration level of regulatory T (Treg) cells and M2-type macrophages (P < 0.05). Conclusion: Patients with high PKMYT1 expression have a poorer prognosis, and the mechanism may be related to tumor immune infiltration and cell cycle regulation. PKMYT1 is expected to be a potential target for the diagnosis and treatment of glioma.
2025, 32(5):510-517.
Abstract:
[Abstract] Objective: To investigate the expression, function, and clinical significance of CD24 in testicular germ cell tumors (TGCT). Methods: This study included 204 testicular germ cell tumor (TGCT) patients from the TCGA database and the TGCT-Changhai testicular germ cell tumor cohort (Changhai Hospital cohort). Prognostic analysis and multivariate analysis were employed to evaluate the association between CD24 expression and clinical characteristics. Immunohistochemistry (IHC) staining of tumor tissues was used to elucidate the mechanism by which CD24 regulated the tumor immune microenvironment (TIME) in TGCT. Finally, by analyzing the diffrences in PD-L1 expression levels and tumor-associated macrophage (TAM) M2-type cell infiltration rates between CD24 high-expression and low-expression groups, and employing the TIDE algorithm, we investigated the correlation between CD24 expression levels and immune escape scores as well as immunotherapy response rates. Results: Analysis of the TCGA database revealed that CD24 expression was significantly upregulated in TGCT with high clinical staging and M-stage (P < 0.05). Compared to adjacent normal tissues, CD24 expression was significantly elevated in both primary and metastatic TGCT tissues (P < 0.05). Significant differences in CD24 expression levels were observed across TNM stages and tumor progression statuses (all P < 0.05). Univariate logistic regression analysis identified CD24 as a predictive factor for clinical outcomes in TGCT patients (OR = 0.135, 95% CI [0.035, 0.516], P = 0.003), and multivariate analysis further confirmed its role as an independent predictor (OR = 0.057, 95% CI [0.005, 0.624], P = 0.019). In TGCT tissues, CD24 mRNA levels correlated with immune cell markers CD206 and CD70 (all P < 0.05). Additionally, CD24 expression levels demonstrated significant predictive value in immune escape scoring and immunotherapy response rate assessments. Conclusions: CD24 is highly expressed in TGCT tissues and its expression is significantly correlated with the prognosis of TGCT patients, which makes it a potential new target point of biotherapy for testicular germ cell tumor patients.
[Abstract] Objective: To investigate the expression, function, and clinical significance of CD24 in testicular germ cell tumors (TGCT). Methods: This study included 204 testicular germ cell tumor (TGCT) patients from the TCGA database and the TGCT-Changhai testicular germ cell tumor cohort (Changhai Hospital cohort). Prognostic analysis and multivariate analysis were employed to evaluate the association between CD24 expression and clinical characteristics. Immunohistochemistry (IHC) staining of tumor tissues was used to elucidate the mechanism by which CD24 regulated the tumor immune microenvironment (TIME) in TGCT. Finally, by analyzing the diffrences in PD-L1 expression levels and tumor-associated macrophage (TAM) M2-type cell infiltration rates between CD24 high-expression and low-expression groups, and employing the TIDE algorithm, we investigated the correlation between CD24 expression levels and immune escape scores as well as immunotherapy response rates. Results: Analysis of the TCGA database revealed that CD24 expression was significantly upregulated in TGCT with high clinical staging and M-stage (P < 0.05). Compared to adjacent normal tissues, CD24 expression was significantly elevated in both primary and metastatic TGCT tissues (P < 0.05). Significant differences in CD24 expression levels were observed across TNM stages and tumor progression statuses (all P < 0.05). Univariate logistic regression analysis identified CD24 as a predictive factor for clinical outcomes in TGCT patients (OR = 0.135, 95% CI [0.035, 0.516], P = 0.003), and multivariate analysis further confirmed its role as an independent predictor (OR = 0.057, 95% CI [0.005, 0.624], P = 0.019). In TGCT tissues, CD24 mRNA levels correlated with immune cell markers CD206 and CD70 (all P < 0.05). Additionally, CD24 expression levels demonstrated significant predictive value in immune escape scoring and immunotherapy response rate assessments. Conclusions: CD24 is highly expressed in TGCT tissues and its expression is significantly correlated with the prognosis of TGCT patients, which makes it a potential new target point of biotherapy for testicular germ cell tumor patients.
2025, 32(5):518-524.
Abstract:
[Abstract] Objective: To investigate the expression of lysosome-associated membrane protein 3 (LAMP3) and activating transcription factor 4 (ATF4) in cervical cancer and their correlation with clinicopathological parameters. Methods: The expression of LAMP3 and ATF4 in normal cervical tissues, cervical intraepithelial lesions, and cervical cancer tissues was detected by SP immunohistochemistry. The relationships between the expression of these two proteins and patient clinicopathological parameters were analyzed, as well as the correlation between LAMP3 and ATF4 expression. Results: LAMP3 was negative or lowly expressed in both normal cervix tissues and high-grade squamous intraepithelial lesions, but highly expressed in cervical cancer tissues (38.3%), showing a statistically significant difference (χ2 = 14.113, P = 0.001). ATF4 was highly expressed in 26.7% of the normal cervix tissues, 10.0% of the high-grade squamous intraepithelial lesions, and 58.3% in the cervical cancer tissues, also showing a significant difference (χ2 = 11.078, P = 0.004). In cervical cancer, LAMP3 expression was significantly associated with FIGO stage (χ2 = 10.139, P = 0.006) and lymph node metastasis (χ2 = 8.475, P = 0.004); ATF4 expression was significantly associated with tumor size (χ2 = 4.578, P = 0.032), FIGO stage (χ2 = 8.971, P = 0.009), and lymph node metastasis (χ2 = 7.881, P = 0.005). There was a positive correlation between the expression of LAMP3 and ATF4 in cervical cancer tissues (r = 0.388, P = 0.002). Conclusion: LAMP3 and ATF4 are highly expressed in cervical cancer tissues and are positively correlated. Both of them play important roles in the development and progression of cervical cancer and could serve as potential therapeutic targets for cervical cancer treatment.
[Abstract] Objective: To investigate the expression of lysosome-associated membrane protein 3 (LAMP3) and activating transcription factor 4 (ATF4) in cervical cancer and their correlation with clinicopathological parameters. Methods: The expression of LAMP3 and ATF4 in normal cervical tissues, cervical intraepithelial lesions, and cervical cancer tissues was detected by SP immunohistochemistry. The relationships between the expression of these two proteins and patient clinicopathological parameters were analyzed, as well as the correlation between LAMP3 and ATF4 expression. Results: LAMP3 was negative or lowly expressed in both normal cervix tissues and high-grade squamous intraepithelial lesions, but highly expressed in cervical cancer tissues (38.3%), showing a statistically significant difference (χ2 = 14.113, P = 0.001). ATF4 was highly expressed in 26.7% of the normal cervix tissues, 10.0% of the high-grade squamous intraepithelial lesions, and 58.3% in the cervical cancer tissues, also showing a significant difference (χ2 = 11.078, P = 0.004). In cervical cancer, LAMP3 expression was significantly associated with FIGO stage (χ2 = 10.139, P = 0.006) and lymph node metastasis (χ2 = 8.475, P = 0.004); ATF4 expression was significantly associated with tumor size (χ2 = 4.578, P = 0.032), FIGO stage (χ2 = 8.971, P = 0.009), and lymph node metastasis (χ2 = 7.881, P = 0.005). There was a positive correlation between the expression of LAMP3 and ATF4 in cervical cancer tissues (r = 0.388, P = 0.002). Conclusion: LAMP3 and ATF4 are highly expressed in cervical cancer tissues and are positively correlated. Both of them play important roles in the development and progression of cervical cancer and could serve as potential therapeutic targets for cervical cancer treatment.
2025, 32(5):525-530.
Abstract:
[摘 要] 软骨肉瘤是第二常见的原发性骨恶性肿瘤，因对放疗和化疗不敏感，患者整体预后较差。靶向代谢治疗作为新型手 段用于软骨肉瘤治疗，展现出广阔应用前景。本文全面综述软骨肉瘤的代谢特性和靶向治疗的最新研究进展。研究揭示， GLUT1介导的糖摄取增强与LDHA驱动的乳酸堆积，协同促进软骨肉瘤细胞发生免疫逃逸；脂质代谢异常涉及Hedgehog通路 与胆固醇合成的双向调控，IDH突变导致SCAP/SREBP轴异常激活引发胆固醇过载；氨基酸代谢方面，依靠谷氨酰胺分解与支链 氨基酸代谢网络来维持生物合成；线粒体TOMM20过表达和SIRT1-HIF-2α轴激活，可增强氧化磷酸化并抑制凋亡。针对上述特 征，联合靶向EGFR与糖酵解、调控miR-125b/ErbB2通路、抑制胆固醇合成及诱导线粒体-内质网协同凋亡等策略，已展现出应用 潜力。然而，代谢异质性引发的治疗抵抗、缺乏特异性标志物及临床转化证据不足，仍是该领域面临的重大挑战。未来，需借助 多组学指导的个体化治疗及新型多靶点药物研发实现突破。
[摘 要] 软骨肉瘤是第二常见的原发性骨恶性肿瘤，因对放疗和化疗不敏感，患者整体预后较差。靶向代谢治疗作为新型手 段用于软骨肉瘤治疗，展现出广阔应用前景。本文全面综述软骨肉瘤的代谢特性和靶向治疗的最新研究进展。研究揭示， GLUT1介导的糖摄取增强与LDHA驱动的乳酸堆积，协同促进软骨肉瘤细胞发生免疫逃逸；脂质代谢异常涉及Hedgehog通路 与胆固醇合成的双向调控，IDH突变导致SCAP/SREBP轴异常激活引发胆固醇过载；氨基酸代谢方面，依靠谷氨酰胺分解与支链 氨基酸代谢网络来维持生物合成；线粒体TOMM20过表达和SIRT1-HIF-2α轴激活，可增强氧化磷酸化并抑制凋亡。针对上述特 征，联合靶向EGFR与糖酵解、调控miR-125b/ErbB2通路、抑制胆固醇合成及诱导线粒体-内质网协同凋亡等策略，已展现出应用 潜力。然而，代谢异质性引发的治疗抵抗、缺乏特异性标志物及临床转化证据不足，仍是该领域面临的重大挑战。未来，需借助 多组学指导的个体化治疗及新型多靶点药物研发实现突破。
2025, 32(5):531-537.
Abstract:
[摘 要] 近年来，免疫治疗在肿瘤治疗领域发挥着不可或缺的作用。进一步研究发现，在固有免疫中发挥重要作用的NK细胞也存在类似适 应性免疫细胞的免疫记忆，相较于原始NK细胞，记忆性NK细胞的寿命更长，抗肿瘤作用也更加显著。现已有多项临床试验和临床前试验证明 记忆性NK细胞抗肿瘤治疗有效。本文详述记忆性NK细胞提出的相关研究及存在问题，阐述记忆性NK细胞杀伤机制，并介绍其在肿瘤治疗方 面的应用，涵盖CIML-NK细胞过继免疫疗法、CAR-NK细胞免疫疗法、联合单克隆抗体治疗、CAR样NK 细胞技术等，并列举各疗法的临床试验 情况。记忆性 NK 细胞优势独特，虽目前尚未完全应用于临床，但在肿瘤免疫治疗中前景广阔，未来通过对记忆性NK细胞优化扩增、降低成本等 方面的深入探索，有望在临床中实现更好的肿瘤免疫治疗。
[摘 要] 近年来，免疫治疗在肿瘤治疗领域发挥着不可或缺的作用。进一步研究发现，在固有免疫中发挥重要作用的NK细胞也存在类似适 应性免疫细胞的免疫记忆，相较于原始NK细胞，记忆性NK细胞的寿命更长，抗肿瘤作用也更加显著。现已有多项临床试验和临床前试验证明 记忆性NK细胞抗肿瘤治疗有效。本文详述记忆性NK细胞提出的相关研究及存在问题，阐述记忆性NK细胞杀伤机制，并介绍其在肿瘤治疗方 面的应用，涵盖CIML-NK细胞过继免疫疗法、CAR-NK细胞免疫疗法、联合单克隆抗体治疗、CAR样NK 细胞技术等，并列举各疗法的临床试验 情况。记忆性 NK 细胞优势独特，虽目前尚未完全应用于临床，但在肿瘤免疫治疗中前景广阔，未来通过对记忆性NK细胞优化扩增、降低成本等 方面的深入探索，有望在临床中实现更好的肿瘤免疫治疗。
2025, 32(5):538-543.
Abstract:
[摘 要] 核受体亚家族4A成员1（NR4A1）是一个重要转录因子，在细胞的增殖、凋亡调控、肿瘤发生、炎症、代谢及免疫调节等 生命活动中发挥重要作用，其功能受到磷酸化、蛋白质相互作用等多种途径的调控。近年来发现，NR4A1在T细胞增殖分化及耗 竭和功能障碍中发挥关键作用。NR4A1缺失可提高T细胞的增殖和活化效率且对肿瘤发生产生影响。另外，NR4A1还能通过 影响其他免疫细胞来影响免疫微环境的炎症反应及抗原提呈效率，从而影响肿瘤的发生、发展。因此，NR4A1抑制剂为肿瘤免疫 靶向药物提供新思路，可通过抑制NR4A1表达来活化或增强T细胞的功能，增强其对肿瘤的杀伤力。目前，NR4A1作为肿瘤免 疫靶点对肿瘤的作用仍在探索阶段，还需进一步的研究并将研究成果向临床应用转化。未来的研究将进一步探索NR4A1在肿 瘤中的调节机制，从而为开发新型免疫疗法提供更多有效信息。
[摘 要] 核受体亚家族4A成员1（NR4A1）是一个重要转录因子，在细胞的增殖、凋亡调控、肿瘤发生、炎症、代谢及免疫调节等 生命活动中发挥重要作用，其功能受到磷酸化、蛋白质相互作用等多种途径的调控。近年来发现，NR4A1在T细胞增殖分化及耗 竭和功能障碍中发挥关键作用。NR4A1缺失可提高T细胞的增殖和活化效率且对肿瘤发生产生影响。另外，NR4A1还能通过 影响其他免疫细胞来影响免疫微环境的炎症反应及抗原提呈效率，从而影响肿瘤的发生、发展。因此，NR4A1抑制剂为肿瘤免疫 靶向药物提供新思路，可通过抑制NR4A1表达来活化或增强T细胞的功能，增强其对肿瘤的杀伤力。目前，NR4A1作为肿瘤免 疫靶点对肿瘤的作用仍在探索阶段，还需进一步的研究并将研究成果向临床应用转化。未来的研究将进一步探索NR4A1在肿 瘤中的调节机制，从而为开发新型免疫疗法提供更多有效信息。
2025, 32(5):544-550.
Abstract:
[摘 要] 鞘氨醇激酶（SphK）通过催化鞘氨醇（Sph）生成1-磷酸鞘氨醇（S1P），在调控细胞生物学功能及介导肿瘤迁移、侵袭和 耐药等恶性行为中发挥关键作用，其相关机制近年受到广泛关注。本文系统总结了SphK/S1P信号通路在肿瘤发展中的促瘤机 制，包括通过激活上皮间充质转化（EMT）促进肿瘤细胞侵袭与转移，参与炎症驱动的肿瘤进展，介导促炎信号与调控炎症因子表 达，介导肿瘤相关炎症反应以及与EGFR通路形成功能串扰，增强细胞生长和存活能力；此外还深入讨论了其在调控血脑屏障通 透性及促进脑转移发生过程中的关键机制，旨在深入解析SphK/S1P信号通路在肿瘤转移和侵袭中的作用，为恶性肿瘤患者的治 疗提供潜在的靶点。
[摘 要] 鞘氨醇激酶（SphK）通过催化鞘氨醇（Sph）生成1-磷酸鞘氨醇（S1P），在调控细胞生物学功能及介导肿瘤迁移、侵袭和 耐药等恶性行为中发挥关键作用，其相关机制近年受到广泛关注。本文系统总结了SphK/S1P信号通路在肿瘤发展中的促瘤机 制，包括通过激活上皮间充质转化（EMT）促进肿瘤细胞侵袭与转移，参与炎症驱动的肿瘤进展，介导促炎信号与调控炎症因子表 达，介导肿瘤相关炎症反应以及与EGFR通路形成功能串扰，增强细胞生长和存活能力；此外还深入讨论了其在调控血脑屏障通 透性及促进脑转移发生过程中的关键机制，旨在深入解析SphK/S1P信号通路在肿瘤转移和侵袭中的作用，为恶性肿瘤患者的治 疗提供潜在的靶点。
2025, 32(5):551-554.
Abstract:
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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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.