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Volume 29,Issue 8,2022 Table of Contents
2022, 29(8):701-707.
DOI: 10.3872/j.issn.1007-385X.2022.08.001
Abstract:
Pyroptosis is a recently-discovered novel regulatory cell death that plays an important role in tumor immunity. Pyroptosis in cancer progression includes immune cell pyroptosis (ICP) and cancer cell pyroptosis (CCP), which may promote or inhibit cancer. The occurrence of ICP can be mediated by both caspase-1 mediated classical pathway and caspase-4/5/11 mediated non-classical pathway. Inflammasome and cytokines IL-18 and IL-1β play important roles in tumor immunity involving ICP. The occurrence of CCP is mediated by GSDME pathway which can be cleaved and activated by caspase-3 and granzyme B. Spontaneous and persistent CCP promotes tumor growth during tumorigenesis, while GSEME activation-mediated CCP has significant anti-tumor effect during chemotherapy and other processes. Pyroptosis can stimulate inflammatory response in tumor microenvironment, improve immunogenicity of tumor cells and promote the occurrence of anti-tumor immunity. Therefore, pyroptosis and its induced inflammatory response play an important role in tumor immunity. Researches in this field may provide new ideas for anti-tumor immunotherapy.
Pyroptosis is a recently-discovered novel regulatory cell death that plays an important role in tumor immunity. Pyroptosis in cancer progression includes immune cell pyroptosis (ICP) and cancer cell pyroptosis (CCP), which may promote or inhibit cancer. The occurrence of ICP can be mediated by both caspase-1 mediated classical pathway and caspase-4/5/11 mediated non-classical pathway. Inflammasome and cytokines IL-18 and IL-1β play important roles in tumor immunity involving ICP. The occurrence of CCP is mediated by GSDME pathway which can be cleaved and activated by caspase-3 and granzyme B. Spontaneous and persistent CCP promotes tumor growth during tumorigenesis, while GSEME activation-mediated CCP has significant anti-tumor effect during chemotherapy and other processes. Pyroptosis can stimulate inflammatory response in tumor microenvironment, improve immunogenicity of tumor cells and promote the occurrence of anti-tumor immunity. Therefore, pyroptosis and its induced inflammatory response play an important role in tumor immunity. Researches in this field may provide new ideas for anti-tumor immunotherapy.
2022, 29(8):708-713.
DOI: 10.3872/j.issn.1007-385X.2022.08.002
Abstract:
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract, which is insensitive to radiotherapy or chemotherapy. In the past two decades, the tyrosine kinase inhibitors (e. g. imatinib) have greatly improved the prognosis of patients with GIST, but primary or secondary drug resistance occurred in a considerable number of patients. Therefore, it is necessary to explore new treatments. With the development of basic and clinical researches in tumor immunotherapies, more and more patients with various tumors have benefited from immunotherapy. However, the application of immunotherapy in the treatment of GIST progressed rather slowly. Although there is some progress in immune checkpoint therapy for GIST, more evidence is required in the future. In the promising fields of immune cell therapy and neoantigen vaccine, no new technology has been introduced into the clinical studies of GIST. Nevertheless, GIST has abundant immune cell infiltration in immune microenvironment, suggesting that GIST may benefit from immunotherapy. Instead of directly using the characteristics of epithelium-derived tumors, immunotherapy studies in GIST should be based on thorough understanding of the unique immune signature of GIST. Only through targeted researches and GIST-specific immunotherapy, could immunotherapy of GIST truly improve the prognosis of patients with GIST.
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract, which is insensitive to radiotherapy or chemotherapy. In the past two decades, the tyrosine kinase inhibitors (e. g. imatinib) have greatly improved the prognosis of patients with GIST, but primary or secondary drug resistance occurred in a considerable number of patients. Therefore, it is necessary to explore new treatments. With the development of basic and clinical researches in tumor immunotherapies, more and more patients with various tumors have benefited from immunotherapy. However, the application of immunotherapy in the treatment of GIST progressed rather slowly. Although there is some progress in immune checkpoint therapy for GIST, more evidence is required in the future. In the promising fields of immune cell therapy and neoantigen vaccine, no new technology has been introduced into the clinical studies of GIST. Nevertheless, GIST has abundant immune cell infiltration in immune microenvironment, suggesting that GIST may benefit from immunotherapy. Instead of directly using the characteristics of epithelium-derived tumors, immunotherapy studies in GIST should be based on thorough understanding of the unique immune signature of GIST. Only through targeted researches and GIST-specific immunotherapy, could immunotherapy of GIST truly improve the prognosis of patients with GIST.
2022, 29(8):714-723.
DOI: 10.3872/j.issn.1007-385X.2022.08.003
Abstract:
Objective: To investigate the impact of activating transcription factor 6 (ATF6) on the immunogenicity of osteosarcoma cells MCA205, and to preliminarily explore the underlying regulatory mechanisms. Methods: The CRISPR-Cas9 technology was utilized to knock out Atf6 gene in MCA205 cells. By using CCK-8 assays, cell energy metabolism assays, flow cytometry, ATP detection kits, interferon-sensitive response element (ISRE) -luciferase reporter cells and qPCR, we analyzed cell viability,mitochondrial oxygen consumption rate (OCR), extracellular acidification rate (ECAR), phosphatidylserine exposure and permeabilization of cell membranes, intracellular calcium mobilization, intracellular and extracellular ATP concentration, IFN-a/b secretion, and the expression of interferon-stimulated genes (ISG) in wild-type (WT) and Atf6-/- MCA205 cells after PBS or tunicamycin (Tm) treatment, respectively. WT or Atf6-/- MCA205 cells were subcutaneously inoculated in immunocompetent mice. Tumor growth kinetics, gene transcription profiles in tumor tissues and activation of local anti-tumor effector T cells of the two groups were compared.WT and Atf6-/- MCA205 cells were simultaneously inoculated on two sides of nu/nu mice. Alternatively, Atf6-/- MCA205 cells were inoculated subcutaneously in immunocompetent mice and Ifnar-/- mice. Tumor growth curves were recorded. Tm-pretreated WT and Atf6-/- MCA205 cells were used to stimulate na?ve mice (without any previous immunostimulation) and prime tumor antigen-specific T cells, respectively. Cells from draining lymph nodes were then collected and boosted in vitro. Activation of antigen-specific T cells of the two groups were compared. At different effector-target ratios, NK cells were mixed with fluorescent dye-prelabeled WT and Atf6-/-MCA205 cells. NK cell-based killing was detected by flow cytometry. Results: Upon PBS or Tm treatment, we haven’t observed any significant differences between WT and Atf6-/- tumor cells in their viability and proliferation, oxidative phosphorylation and glycolysis,ionomycin-triggered intracellular calcium mobilization, intracellular and extracellular ATP content and IFN-a/b secretion. Upon Tm treatment, the death ratio of Atf6-/- tumor cells was significantly lower than that of WT tumor cells (P<0.01). In immunocompetent mice,the growth of Atf6-/- tumors was significantly slower than that of WT tumors (P<0.05). However, their differences in growth kinetics were largely diminished in nu/nu mice. The growth of Atf6-/- tumors in Ifnar-/- mice was slightly faster than that in immunocompetent mice (P<0.05). The expression of immune response-related genes and the activation of effector T cells in Atf6-/- tumors were significantly higher than those in WT tumors (P<0.05). Compared with that of WT MCA205 cells, Atf6-/- MCA205 cells were more sensitive to NK cell-mediated cytolysis. Upon Tm preconditioning, Atf6-/- MCA205 cells expressed more Irf3 and Irf7 and can stimulate more IFN-g production from T cells in the prime-boost setting than WT cells. Conclusion: Blocking ATF6 signaling pathway can significantly enhance the immunogenicity of MCA205 cells, promote immune surveillance and delay tumor progression.
Objective: To investigate the impact of activating transcription factor 6 (ATF6) on the immunogenicity of osteosarcoma cells MCA205, and to preliminarily explore the underlying regulatory mechanisms. Methods: The CRISPR-Cas9 technology was utilized to knock out Atf6 gene in MCA205 cells. By using CCK-8 assays, cell energy metabolism assays, flow cytometry, ATP detection kits, interferon-sensitive response element (ISRE) -luciferase reporter cells and qPCR, we analyzed cell viability,mitochondrial oxygen consumption rate (OCR), extracellular acidification rate (ECAR), phosphatidylserine exposure and permeabilization of cell membranes, intracellular calcium mobilization, intracellular and extracellular ATP concentration, IFN-a/b secretion, and the expression of interferon-stimulated genes (ISG) in wild-type (WT) and Atf6-/- MCA205 cells after PBS or tunicamycin (Tm) treatment, respectively. WT or Atf6-/- MCA205 cells were subcutaneously inoculated in immunocompetent mice. Tumor growth kinetics, gene transcription profiles in tumor tissues and activation of local anti-tumor effector T cells of the two groups were compared.WT and Atf6-/- MCA205 cells were simultaneously inoculated on two sides of nu/nu mice. Alternatively, Atf6-/- MCA205 cells were inoculated subcutaneously in immunocompetent mice and Ifnar-/- mice. Tumor growth curves were recorded. Tm-pretreated WT and Atf6-/- MCA205 cells were used to stimulate na?ve mice (without any previous immunostimulation) and prime tumor antigen-specific T cells, respectively. Cells from draining lymph nodes were then collected and boosted in vitro. Activation of antigen-specific T cells of the two groups were compared. At different effector-target ratios, NK cells were mixed with fluorescent dye-prelabeled WT and Atf6-/-MCA205 cells. NK cell-based killing was detected by flow cytometry. Results: Upon PBS or Tm treatment, we haven’t observed any significant differences between WT and Atf6-/- tumor cells in their viability and proliferation, oxidative phosphorylation and glycolysis,ionomycin-triggered intracellular calcium mobilization, intracellular and extracellular ATP content and IFN-a/b secretion. Upon Tm treatment, the death ratio of Atf6-/- tumor cells was significantly lower than that of WT tumor cells (P<0.01). In immunocompetent mice,the growth of Atf6-/- tumors was significantly slower than that of WT tumors (P<0.05). However, their differences in growth kinetics were largely diminished in nu/nu mice. The growth of Atf6-/- tumors in Ifnar-/- mice was slightly faster than that in immunocompetent mice (P<0.05). The expression of immune response-related genes and the activation of effector T cells in Atf6-/- tumors were significantly higher than those in WT tumors (P<0.05). Compared with that of WT MCA205 cells, Atf6-/- MCA205 cells were more sensitive to NK cell-mediated cytolysis. Upon Tm preconditioning, Atf6-/- MCA205 cells expressed more Irf3 and Irf7 and can stimulate more IFN-g production from T cells in the prime-boost setting than WT cells. Conclusion: Blocking ATF6 signaling pathway can significantly enhance the immunogenicity of MCA205 cells, promote immune surveillance and delay tumor progression.
2022, 29(8):724-731.
DOI: 10.3872/j.issn.1007-385X.2022.08.004
Abstract:
Objective: To explore the mechanism of tripartite motif-containing 59 (TRIM59) regulating the proliferation, cell cycle,apoptosis, migration and invasion of human skin melanoma cells SK-MEL-2, and its relationship with Bcl2-associated transcription factor (BCLAF1). Methods: qPCR and WB assay were used to measure the mRNA and protein expression of TRIM59 in human epidermal melanocytes HEMN-LP, human skin melanoma cells SK-MEL-2, UACC903, A375, and 36 cases of human skin melanoma tissues collected from February 2019 to July 2021 in Xingtai people's Hospital. Si-con and si-TRIM59 were transfected into SK-MEL-2 cells using liposomes. WB assay was used to detect the effects of interference with the expression of TRIM59 on cyclin D1 (CCND1),cyclin-dependent kinase 2 (CDK2), tumor suppressor protein gene (TP53) and BCLAF1 protein expression. CCK-8 assay, flow cytometry, scratch test and Transwell test were used to detect cell activity, apoptosis, migration and invasion. The binding ability of TRIM59 protein and BCLAF1 was detected by Co-IP assay. Results: Compared with the HEMN-LP group, the mRNA and protein expression of TRIM59 BCLAF1 protein in SK-MEL-2, UACC903and A375 cells were significantly increased (P<0.05). The expression level of TRIM59 in SK-MEL-2 cells were the highest. Compared with the si-con group and the Normal group, after silencing TRIM59,the activity of SK-MEL-2 cells was significantly decreased; the G2 phase of the cell cycle was blocked; the protein expressions of CCND1 and CDK2 were decreased significantly; the TP53 protein and apoptosis rate were significantly increased; the scratch inhibition rate was significantly increased, and the numbers of migration and invasion cells were significantly decreased. (all P<0.05).The results of co-immunoprecipitation experiments showed that there was a protein-binding relationship between TRIM59 and BCLAF1. There was a significant positive correlation between TRIM59 and BCLAF1 expression in tumor tissues (r=0.878, P<0.001).Conclusion: Silencing TRIM59 expression could inhibit the proliferation, migration and invasion of skin cutaneous melanoma cells,promote apoptosis and inhibit the malignant biological behaviors of SK-MEL-2 cells. The mechanism may be related to the binding of TRIM59 with BCLAF1.
Objective: To explore the mechanism of tripartite motif-containing 59 (TRIM59) regulating the proliferation, cell cycle,apoptosis, migration and invasion of human skin melanoma cells SK-MEL-2, and its relationship with Bcl2-associated transcription factor (BCLAF1). Methods: qPCR and WB assay were used to measure the mRNA and protein expression of TRIM59 in human epidermal melanocytes HEMN-LP, human skin melanoma cells SK-MEL-2, UACC903, A375, and 36 cases of human skin melanoma tissues collected from February 2019 to July 2021 in Xingtai people's Hospital. Si-con and si-TRIM59 were transfected into SK-MEL-2 cells using liposomes. WB assay was used to detect the effects of interference with the expression of TRIM59 on cyclin D1 (CCND1),cyclin-dependent kinase 2 (CDK2), tumor suppressor protein gene (TP53) and BCLAF1 protein expression. CCK-8 assay, flow cytometry, scratch test and Transwell test were used to detect cell activity, apoptosis, migration and invasion. The binding ability of TRIM59 protein and BCLAF1 was detected by Co-IP assay. Results: Compared with the HEMN-LP group, the mRNA and protein expression of TRIM59 BCLAF1 protein in SK-MEL-2, UACC903and A375 cells were significantly increased (P<0.05). The expression level of TRIM59 in SK-MEL-2 cells were the highest. Compared with the si-con group and the Normal group, after silencing TRIM59,the activity of SK-MEL-2 cells was significantly decreased; the G2 phase of the cell cycle was blocked; the protein expressions of CCND1 and CDK2 were decreased significantly; the TP53 protein and apoptosis rate were significantly increased; the scratch inhibition rate was significantly increased, and the numbers of migration and invasion cells were significantly decreased. (all P<0.05).The results of co-immunoprecipitation experiments showed that there was a protein-binding relationship between TRIM59 and BCLAF1. There was a significant positive correlation between TRIM59 and BCLAF1 expression in tumor tissues (r=0.878, P<0.001).Conclusion: Silencing TRIM59 expression could inhibit the proliferation, migration and invasion of skin cutaneous melanoma cells,promote apoptosis and inhibit the malignant biological behaviors of SK-MEL-2 cells. The mechanism may be related to the binding of TRIM59 with BCLAF1.
2022, 29(8):732-740.
DOI: 10.3872/j.issn.1007-385X.2022.08.005
Abstract:
Objective: To investigate the effects of miR-124 on the proliferation, apoptosis, migration and invasion of renal cell carcinoma (RCC) cells by regulating the Jagged1 (JAG1)/Notch signaling pathway. Methods: The RCC tissues and paracancerous tissues of 38 RCC patients treated in Wuhan Third Hospital from June 2018 to October 2021 were collected, and RCC cells (Caki-2,A498, ACHN, 786-O, OS-RC-2) and human normal kidney cells (293T) were cultured in vitro. The expression levels of miR-124 and JAG1 proteins in RCC tissues and cells were detected by immunohistochemistry, qPCR and WB assay. OS-RC-2 cells, which had the greatest difference in expression of miR-124 with that of 293T cells, were selected for transfection and divided into control group, NC mimic group, miR-124 mimic group, miR-124 mimic+pcDNA group and miR-124 mimic+pc-JAG1 group according to the difference in transfectants. The relationship between miR-124 and JAG1 was verified by dual-luciferase reporter gene experiments; the expressions of miR-124 and JAG1 mRNA were detected by qPCR; the protein expression of JAG1 was analyzed by immunohistochemistry method; WB assay was performed to measure the expressions of JAG1, apoptosis-related proteins (cleaved caspase-3, BAX, Bcl2) and Notch signaling pathway-related proteins (NICD, HES1 and HES5); MTT method was performed to measure the proliferation of OS-RC-2 cells; Transwell assay was performed to measure the migration and invasion of OS-RC-2 cells;and flow cytometry was performed to measure the apoptosis of OS-RC-2 cells. Results:Compared with paracancerous tissues, the expression of miR-124 in RCC tissues decreased, and the expressions of JAG1 mRNA and protein increased (all P<0.01); compared with 293T cells, the levels of miR-124 decreased while the expressions of JAG1 mRNA and protein increased in Caki-2, A498, ACHN,786-O and OS-RC-2 cells (all P<0.05); miR-124 directly negatively regulated JAG1. Compared with the Control group and the NC mimic group, the expression level of miR-124, the apoptosis rate and the expressions of cleaved caspase-3 and BAX proteins in the miR-124 mimic group increased; the expressions of JAG1 mRNA and protein decreased; the cell viability (24, 48, 72 h) decreased; the numbers of migrating and invasive cells decreased; the expressions of Bcl2 and NICD, HES1, HES5 proteins decreased (all P<0.05).Compared with the miR-124 mimic+pcDNA group and the miR-124 mimic group, the expression level of miR-124, the apoptosis rate and the expressions of cleaved caspase-3 and BAX proteins in the miR-124 mimic+pc-JAG1 group decreased; the expressions of JAG1 mRNA and protein increased; the cell viability (24, 48, 72 h) increased; the numbers of migrating and invasive cells increased and the expressions of Bcl2 and NICD, HES1, HES5 proteins increased (all P<0.05). Conclusion: miR-124 reduced the proliferation, migrationand invasion abilities of RCC OS-RC-2 cells and promoted apoptosis by downregulating JAG1 and inhibiting the Notch signaling pathway.
Objective: To investigate the effects of miR-124 on the proliferation, apoptosis, migration and invasion of renal cell carcinoma (RCC) cells by regulating the Jagged1 (JAG1)/Notch signaling pathway. Methods: The RCC tissues and paracancerous tissues of 38 RCC patients treated in Wuhan Third Hospital from June 2018 to October 2021 were collected, and RCC cells (Caki-2,A498, ACHN, 786-O, OS-RC-2) and human normal kidney cells (293T) were cultured in vitro. The expression levels of miR-124 and JAG1 proteins in RCC tissues and cells were detected by immunohistochemistry, qPCR and WB assay. OS-RC-2 cells, which had the greatest difference in expression of miR-124 with that of 293T cells, were selected for transfection and divided into control group, NC mimic group, miR-124 mimic group, miR-124 mimic+pcDNA group and miR-124 mimic+pc-JAG1 group according to the difference in transfectants. The relationship between miR-124 and JAG1 was verified by dual-luciferase reporter gene experiments; the expressions of miR-124 and JAG1 mRNA were detected by qPCR; the protein expression of JAG1 was analyzed by immunohistochemistry method; WB assay was performed to measure the expressions of JAG1, apoptosis-related proteins (cleaved caspase-3, BAX, Bcl2) and Notch signaling pathway-related proteins (NICD, HES1 and HES5); MTT method was performed to measure the proliferation of OS-RC-2 cells; Transwell assay was performed to measure the migration and invasion of OS-RC-2 cells;and flow cytometry was performed to measure the apoptosis of OS-RC-2 cells. Results:Compared with paracancerous tissues, the expression of miR-124 in RCC tissues decreased, and the expressions of JAG1 mRNA and protein increased (all P<0.01); compared with 293T cells, the levels of miR-124 decreased while the expressions of JAG1 mRNA and protein increased in Caki-2, A498, ACHN,786-O and OS-RC-2 cells (all P<0.05); miR-124 directly negatively regulated JAG1. Compared with the Control group and the NC mimic group, the expression level of miR-124, the apoptosis rate and the expressions of cleaved caspase-3 and BAX proteins in the miR-124 mimic group increased; the expressions of JAG1 mRNA and protein decreased; the cell viability (24, 48, 72 h) decreased; the numbers of migrating and invasive cells decreased; the expressions of Bcl2 and NICD, HES1, HES5 proteins decreased (all P<0.05).Compared with the miR-124 mimic+pcDNA group and the miR-124 mimic group, the expression level of miR-124, the apoptosis rate and the expressions of cleaved caspase-3 and BAX proteins in the miR-124 mimic+pc-JAG1 group decreased; the expressions of JAG1 mRNA and protein increased; the cell viability (24, 48, 72 h) increased; the numbers of migrating and invasive cells increased and the expressions of Bcl2 and NICD, HES1, HES5 proteins increased (all P<0.05). Conclusion: miR-124 reduced the proliferation, migrationand invasion abilities of RCC OS-RC-2 cells and promoted apoptosis by downregulating JAG1 and inhibiting the Notch signaling pathway.
2022, 29(8):741-749.
DOI: 10.3872/j.issn.1007-385X.2022.08.006
Abstract:
Objective: To investigate the expression level and clinical significance of lncRNA MIR17HG in cervical cancer tissues and cells, and to analyze its effect on the malignant biological behaviors of cervical cancer HeLa cells and the growth of transplanted tumors in nude mice and its possible mechanism. Methods: The TCGA database was used to analyze the expression levels of MIR17HG and TRIM25 in cervical cancer tissues, and to analyze the correlation between their expression levels and the clinicopathological characteristics of patients. The tumor tissues and paracancerous tissues of 30 cervical cancer patients admitted to Qilu Hospital of Shandong University from August 2019 to December 2020 were collected. Human normal cervical epithelial End1/E6E7 cells and human breast cancer cells HeLa, C33A, CasKi and SiHa were cultured in vitro. qPCR was used to detect the expression level of MIR17HG in cervical cancer tissues and cells. The MIR17HG overexpression plasmid or knockdown plasmid was transfected into cervical cancer HeLa cells by liposomes respectively, and then the impact of MIR17HG on the proliferation, colony formation,migration, and invasion abilities on HeLa cells were detected by CCK-8 assay, colony formation assay and Transwell assay,respectively. The targeted regulation of MIR17HG on TRIM25 was predicted by ENCORI and verified by qPCR and WB methods.Targetscan and fluorescent reporter systems were used to verify the targeting relationship between miR-377 and TRIM25. WB method was used to detect the effect of MIR17HG on the expression of AKT signaling pathway-related proteins in HeLa cells. A nude mouse xenograft model of MIR17HG overexpressing HeLa cells was constructed, and the growth of the transplanted tumor was observed.Results: Both MIR17HG and TRIM25 mRNA were highly expressed in cervical cancer tissues (both P<0.05), and the expression level of MIR17HG in cervical cancer cells was higher than that in human normal cervical epithelial cells (P<0.01 or P<0.001). The high expression of MIR17HG and TRIM25 was associated with the malignancy of cervical cancer (P<0.05). Compared with the control group, the proliferation, colony formation, migration, and invasion abilities of HeLa cells in the MIR17HG overexpression group were significantly increased, while the opposite was true in the MIR17HG knockdown group (P<0.05 or P<0.01). MIR17HG may upregulate the expression of TRIM25 by inhibiting miR-377. The expression levels of AKT signaling pathway-related proteins in HeLa cells in the MIR17HG overexpression group were increased. The growth level of xenograft tumors in the MIR17HG overexpression group was higher than that in the control group (P<0.01). Conclusion: MIR17HG is highly expressed in cervical cancer tissues and cells. Overexpression of MIR17HG can promote the malignant biological behaviors of HeLa cells and accelerate the growth of transplanted tumors in nude mice. MIR17HG may exert its cancer-promoting effect by inhibiting miR-377 and upregulating TRIM25 to activate the AKT pathway.
Objective: To investigate the expression level and clinical significance of lncRNA MIR17HG in cervical cancer tissues and cells, and to analyze its effect on the malignant biological behaviors of cervical cancer HeLa cells and the growth of transplanted tumors in nude mice and its possible mechanism. Methods: The TCGA database was used to analyze the expression levels of MIR17HG and TRIM25 in cervical cancer tissues, and to analyze the correlation between their expression levels and the clinicopathological characteristics of patients. The tumor tissues and paracancerous tissues of 30 cervical cancer patients admitted to Qilu Hospital of Shandong University from August 2019 to December 2020 were collected. Human normal cervical epithelial End1/E6E7 cells and human breast cancer cells HeLa, C33A, CasKi and SiHa were cultured in vitro. qPCR was used to detect the expression level of MIR17HG in cervical cancer tissues and cells. The MIR17HG overexpression plasmid or knockdown plasmid was transfected into cervical cancer HeLa cells by liposomes respectively, and then the impact of MIR17HG on the proliferation, colony formation,migration, and invasion abilities on HeLa cells were detected by CCK-8 assay, colony formation assay and Transwell assay,respectively. The targeted regulation of MIR17HG on TRIM25 was predicted by ENCORI and verified by qPCR and WB methods.Targetscan and fluorescent reporter systems were used to verify the targeting relationship between miR-377 and TRIM25. WB method was used to detect the effect of MIR17HG on the expression of AKT signaling pathway-related proteins in HeLa cells. A nude mouse xenograft model of MIR17HG overexpressing HeLa cells was constructed, and the growth of the transplanted tumor was observed.Results: Both MIR17HG and TRIM25 mRNA were highly expressed in cervical cancer tissues (both P<0.05), and the expression level of MIR17HG in cervical cancer cells was higher than that in human normal cervical epithelial cells (P<0.01 or P<0.001). The high expression of MIR17HG and TRIM25 was associated with the malignancy of cervical cancer (P<0.05). Compared with the control group, the proliferation, colony formation, migration, and invasion abilities of HeLa cells in the MIR17HG overexpression group were significantly increased, while the opposite was true in the MIR17HG knockdown group (P<0.05 or P<0.01). MIR17HG may upregulate the expression of TRIM25 by inhibiting miR-377. The expression levels of AKT signaling pathway-related proteins in HeLa cells in the MIR17HG overexpression group were increased. The growth level of xenograft tumors in the MIR17HG overexpression group was higher than that in the control group (P<0.01). Conclusion: MIR17HG is highly expressed in cervical cancer tissues and cells. Overexpression of MIR17HG can promote the malignant biological behaviors of HeLa cells and accelerate the growth of transplanted tumors in nude mice. MIR17HG may exert its cancer-promoting effect by inhibiting miR-377 and upregulating TRIM25 to activate the AKT pathway.
2022, 29(8):750-755.
DOI: 10.3872/j.issn.1007-385X.2022.08.007
Abstract:
Objective: To investigate the expressions of T cell immunoreceptor with Ig and ITIM domain (TIGIT) and CD155 in triple negative breast cancer (TNBC) tissues and their correlations with clinicopathologic features and survival prognosis and to explore their value in the prognosis of TNBC. Methods: A total of 64 eligible female patients who underwent surgical resection and were diagnosed by pathology in the Second Affiliated Hospital of Fujian Medical University from January 2014 to December 2018were enrolled, and their tumor tissues collected. Immunohistochemistry was used to detect the expressions of TIGIT and CD155 in TNBC tissues. The clinicopathological data of the enrolled patients were collected and their survival prognosis was followed up. Chi-square test or Fisher's exact test was used to analyze the relationship between the expressions of TIGIT and CD155 and the clinicopathological characteristics. Kaplan-Meier survival curve, Logrank test and Cox regression analysis were used to investigate the relationship between the expressions of TIGIT and CD155 and the prognosis.Results: The positive expression rates of TIGIT and CD155 in TNBC were 48.4% (31/64) and 79.9%(51/64) respectively. Both TIGIT and CD155 expressions were correlated with tumor size, lymph node metastasis and tumor stage (all P<0.05), but not with age, menstrual status,histological grade, and Ki-67 (all P>0.05). Survival analysis indicated that both TIGIT and CD155 expressions were significantly associated with poor DFS (all P<0.05), but they were not independent prognostic risk factors for TNBC. Multivariate analysis showed that only TNMstaging was an independent prognostic risk factor for TNBC patients (P<0.05). Conclusion: TIGIT and CD155 are highly expressed in TNBC and are associated with poor pathological parameters and prognosis.
Objective: To investigate the expressions of T cell immunoreceptor with Ig and ITIM domain (TIGIT) and CD155 in triple negative breast cancer (TNBC) tissues and their correlations with clinicopathologic features and survival prognosis and to explore their value in the prognosis of TNBC. Methods: A total of 64 eligible female patients who underwent surgical resection and were diagnosed by pathology in the Second Affiliated Hospital of Fujian Medical University from January 2014 to December 2018were enrolled, and their tumor tissues collected. Immunohistochemistry was used to detect the expressions of TIGIT and CD155 in TNBC tissues. The clinicopathological data of the enrolled patients were collected and their survival prognosis was followed up. Chi-square test or Fisher's exact test was used to analyze the relationship between the expressions of TIGIT and CD155 and the clinicopathological characteristics. Kaplan-Meier survival curve, Logrank test and Cox regression analysis were used to investigate the relationship between the expressions of TIGIT and CD155 and the prognosis.Results: The positive expression rates of TIGIT and CD155 in TNBC were 48.4% (31/64) and 79.9%(51/64) respectively. Both TIGIT and CD155 expressions were correlated with tumor size, lymph node metastasis and tumor stage (all P<0.05), but not with age, menstrual status,histological grade, and Ki-67 (all P>0.05). Survival analysis indicated that both TIGIT and CD155 expressions were significantly associated with poor DFS (all P<0.05), but they were not independent prognostic risk factors for TNBC. Multivariate analysis showed that only TNMstaging was an independent prognostic risk factor for TNBC patients (P<0.05). Conclusion: TIGIT and CD155 are highly expressed in TNBC and are associated with poor pathological parameters and prognosis.
2022, 29(8):756-761.
DOI: 10.3872/j.issn.1007-385X.2022.08.008
Abstract:
衰老已被认为在肿瘤发生发展过程中起到重要的作用，有证据显示衰老可以通过编程基质细胞重塑微环境，从而促 进肿瘤的发生。衰老微环境具有多种成分，其中衰老相关分泌表型（SASP）、细胞外基质（ECM）及免疫细胞是构成衰老微环境的 主要成分，衰老微环境在肿瘤发展不同阶段具有重要的调控作用，然而其潜在意义一直被忽视。加强对衰老微环境构成成分及 其对肿瘤发生发展的作用及其机制展开深入研究，可为促进基于衰老微环境的肿瘤治疗提供新的思路。
衰老已被认为在肿瘤发生发展过程中起到重要的作用，有证据显示衰老可以通过编程基质细胞重塑微环境，从而促 进肿瘤的发生。衰老微环境具有多种成分，其中衰老相关分泌表型（SASP）、细胞外基质（ECM）及免疫细胞是构成衰老微环境的 主要成分，衰老微环境在肿瘤发展不同阶段具有重要的调控作用，然而其潜在意义一直被忽视。加强对衰老微环境构成成分及 其对肿瘤发生发展的作用及其机制展开深入研究，可为促进基于衰老微环境的肿瘤治疗提供新的思路。
2022, 29(8):762-766.
DOI: 10.3872/j.issn.1007-385X.2022.08.009
Abstract:
由于细胞强异质性的存在，血液肿瘤细胞呈现多样性，而这种多样性根源于基因层面的改变。随着精准医学时代的到 来，对于基因层面的研究越来越依赖于层出不穷的二代测序技术。过去十几年的深度测序技术着重于细胞群体层面的整体分析， 不能深入区分异质性的肿瘤细胞差异化的生命活动。近年来新兴的单细胞测序技术大大促进了血液肿瘤异质性研究的发展。本 文着重介绍血液肿瘤发生发展和治疗耐药性中的细胞异质性及其分子机制，以及利用单细胞测序技术开发更精细层次的标志 物、评估临床实验有效性和安全性方面的研究进展，并对其发展前景做了简要展望。
由于细胞强异质性的存在，血液肿瘤细胞呈现多样性，而这种多样性根源于基因层面的改变。随着精准医学时代的到 来，对于基因层面的研究越来越依赖于层出不穷的二代测序技术。过去十几年的深度测序技术着重于细胞群体层面的整体分析， 不能深入区分异质性的肿瘤细胞差异化的生命活动。近年来新兴的单细胞测序技术大大促进了血液肿瘤异质性研究的发展。本 文着重介绍血液肿瘤发生发展和治疗耐药性中的细胞异质性及其分子机制，以及利用单细胞测序技术开发更精细层次的标志 物、评估临床实验有效性和安全性方面的研究进展，并对其发展前景做了简要展望。
2022, 29(8):767-771.
DOI: 10.3872/j.issn.1007-385X.2022.08.010
Abstract:
胰腺癌是一种具有高度侵袭性且预后极差的消化系统恶性肿瘤，其发病的分子机制及更为有效的治疗手段一直是研 究的热点。三结构域（TRIM）蛋白是具有高度保守的RBCC三段结构域的蛋白家族，其中RING-finger结构域赋予了TRIM蛋白 E3泛素连接酶活性，使其能够介导癌基因和肿瘤抑制因子的泛素化降解，从而在胰腺癌的发生发展中发挥重要作用。TRIM家 族蛋白涉及诸多信号通路，同一个TRIM蛋白分子可能直接或间接参与多个信号通路。单独靶向TRIM家族蛋白（如TRIM2、 TRIM14、TRIM15、TRIM21、TRIM29、TRIM47、TRIM59等），以及靶向TRIM11、TRIM31和TRIM37等与吉西他滨等化疗药物联 合应用有望成为治疗胰腺癌的重要方法和新的策略。TRIM家族蛋白在胰腺癌组织中高表达且与预后密切相关，可能作为早期 诊断和预测胰腺癌预后的生物标志物。研究TRIM家族蛋白在胰腺癌发生发展过程中的分子机制及其作用，有助于为胰腺癌患 者的诊断和治疗提供新思路。
胰腺癌是一种具有高度侵袭性且预后极差的消化系统恶性肿瘤，其发病的分子机制及更为有效的治疗手段一直是研 究的热点。三结构域（TRIM）蛋白是具有高度保守的RBCC三段结构域的蛋白家族，其中RING-finger结构域赋予了TRIM蛋白 E3泛素连接酶活性，使其能够介导癌基因和肿瘤抑制因子的泛素化降解，从而在胰腺癌的发生发展中发挥重要作用。TRIM家 族蛋白涉及诸多信号通路，同一个TRIM蛋白分子可能直接或间接参与多个信号通路。单独靶向TRIM家族蛋白（如TRIM2、 TRIM14、TRIM15、TRIM21、TRIM29、TRIM47、TRIM59等），以及靶向TRIM11、TRIM31和TRIM37等与吉西他滨等化疗药物联 合应用有望成为治疗胰腺癌的重要方法和新的策略。TRIM家族蛋白在胰腺癌组织中高表达且与预后密切相关，可能作为早期 诊断和预测胰腺癌预后的生物标志物。研究TRIM家族蛋白在胰腺癌发生发展过程中的分子机制及其作用，有助于为胰腺癌患 者的诊断和治疗提供新思路。
2022, 29(8):772-776.
DOI: 10.3872/j.issn.1007-385X.2022.08.011
Abstract:
Eps15同源结构域蛋白2（EHD2）是EHD动力蛋白超级家族中的一员，可广泛调节受体蛋白，在细胞黏附、细胞形态、 细胞迁移和胞质分裂等细胞活动过程中起着重要作用。作为新型的膜转运蛋白，EHD2通过调控细胞的内吞作用，参与肿瘤发生 发展特别是转移过程。EHD2与乳腺癌、肝癌、食管鳞癌、甲状腺乳头癌、肾透明细胞癌、骨肉瘤等多种癌症密切相关。当EHD2 表达异常会调控膜转运过程及下游信号通路，影响上皮间质转化（EMT）的进程，从而调节细胞的迁移、侵袭能力，与肿瘤的发生 发展及患者的预后密切相关。本文从EHD2蛋白与肿瘤相关的结构和功能特征、EHD2的生物学功能、EHD2在肿瘤发生发展中 的作用及其调控机制、EHD2在肿瘤防治中的意义等方面进行了探讨，认为EHD2是潜在肿瘤治疗靶点。提高对于EHD2在肿瘤 发生发展中的作用及调控机制和评估预后的临床价值的认识，将有助于为寻找新的肿瘤诊断标志物和治疗靶点提供思路。
Eps15同源结构域蛋白2（EHD2）是EHD动力蛋白超级家族中的一员，可广泛调节受体蛋白，在细胞黏附、细胞形态、 细胞迁移和胞质分裂等细胞活动过程中起着重要作用。作为新型的膜转运蛋白，EHD2通过调控细胞的内吞作用，参与肿瘤发生 发展特别是转移过程。EHD2与乳腺癌、肝癌、食管鳞癌、甲状腺乳头癌、肾透明细胞癌、骨肉瘤等多种癌症密切相关。当EHD2 表达异常会调控膜转运过程及下游信号通路，影响上皮间质转化（EMT）的进程，从而调节细胞的迁移、侵袭能力，与肿瘤的发生 发展及患者的预后密切相关。本文从EHD2蛋白与肿瘤相关的结构和功能特征、EHD2的生物学功能、EHD2在肿瘤发生发展中 的作用及其调控机制、EHD2在肿瘤防治中的意义等方面进行了探讨，认为EHD2是潜在肿瘤治疗靶点。提高对于EHD2在肿瘤 发生发展中的作用及调控机制和评估预后的临床价值的认识，将有助于为寻找新的肿瘤诊断标志物和治疗靶点提供思路。
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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.