BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
MicroRNAs are small single-stranded RNA molecules consisting of approximately 22 nucleotides (nt), and have post-transcriptional regulatory functions. By gene chip screening, we previously showed that miR-142-3p was s...MicroRNAs are small single-stranded RNA molecules consisting of approximately 22 nucleotides (nt), and have post-transcriptional regulatory functions. By gene chip screening, we previously showed that miR-142-3p was significantly upregulated in colorectal cancer tissue and was associated with clinicopathological features, compared with matched non-tumor tissue. In this study, we confirmed significant upregulation of miR-142-3p in 60 colorectal cancer samples and three colorectal cancer cell lines by quantitative real-time PCR (qRT-PCR). Using software and network resources, we predicted TCF7 as a target of miR-142-3p, which we confirmed with dual-luciferase assays. By RT-PCR and Western blot analysis, we found miR-142-3p negatively regulates TCF7 expression post-transcriptionally. CCK8 assays and growth curves indicated that overexpression of miR-142-3p in SW480 colorectal cancer cells potently inhibited cell proliferation in vitro. The expression of TCF7 mRNA and protein was upregulated in both colorectal cancer tissues and colorectal cancer cell lines, closely correlating with its function as an oncogene in promoting tumor cell proliferation and inhibiting apoptosis. With TCF7 as a direct target, our results suggested that miR-142-3p may be involved in the regulation of cell proliferation in colorectal cancer.展开更多
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
文摘MicroRNAs are small single-stranded RNA molecules consisting of approximately 22 nucleotides (nt), and have post-transcriptional regulatory functions. By gene chip screening, we previously showed that miR-142-3p was significantly upregulated in colorectal cancer tissue and was associated with clinicopathological features, compared with matched non-tumor tissue. In this study, we confirmed significant upregulation of miR-142-3p in 60 colorectal cancer samples and three colorectal cancer cell lines by quantitative real-time PCR (qRT-PCR). Using software and network resources, we predicted TCF7 as a target of miR-142-3p, which we confirmed with dual-luciferase assays. By RT-PCR and Western blot analysis, we found miR-142-3p negatively regulates TCF7 expression post-transcriptionally. CCK8 assays and growth curves indicated that overexpression of miR-142-3p in SW480 colorectal cancer cells potently inhibited cell proliferation in vitro. The expression of TCF7 mRNA and protein was upregulated in both colorectal cancer tissues and colorectal cancer cell lines, closely correlating with its function as an oncogene in promoting tumor cell proliferation and inhibiting apoptosis. With TCF7 as a direct target, our results suggested that miR-142-3p may be involved in the regulation of cell proliferation in colorectal cancer.
