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
目的:探讨miR-28-3p在三阴性乳腺癌(triple negative breast cancer,TNBC)组织和细胞系中的表达及其对MDA-MB-468细胞恶性生物学行为的影响。方法:收集2013年1月至2014年1月河北医科大学第四医院乳腺中心手术切除的、经病理证实的83例女...目的:探讨miR-28-3p在三阴性乳腺癌(triple negative breast cancer,TNBC)组织和细胞系中的表达及其对MDA-MB-468细胞恶性生物学行为的影响。方法:收集2013年1月至2014年1月河北医科大学第四医院乳腺中心手术切除的、经病理证实的83例女性TNBC患者的癌组织和癌旁组织标本,以及TNBC细胞系MDA-MB-468、HCC-1937、MDA-MB-231、MDA-MB-436、MDA-MB-453和人正常乳腺上皮细胞MCF10A,用qPCR检测组织和细胞系中miR-28-3p的表达水平并分析其表达与患者临床病理特征的相关性。用miR-28-3p抑制剂转染MDA-MB-468细胞后,用CCK-8、流式细胞术、细胞划痕和Transwell实验分别检测miR-28-3p抑制剂对MDA-MB-468细胞增殖、凋亡、侵袭和迁移能力的影响,用Western blotting检测MDA-MB-468细胞中桥接整合因子1(bridging integrator-1,BIN1)蛋白的表达水平。通过生物信息学工具预测miR-28-3p的靶基因BIN1,用双荧光素酶报告基因实验验证miR-28-3p对BIN1的调控作用。结果:TNBC组织及细胞系中miR-28-3p表达水平显著高于癌旁组织及MCF10A细胞(均P<0.01);83例TNBC组织中共有56例(67.47%)高表达miR-28-3p,其高表达与患者的Ki-67表达水平、肿瘤大小和TNM分期密切相关(均P<0.05或P<0.01)。与miR-NC组比较,miR-28-3p抑制剂组MDA-MB-468细胞增殖、侵袭和迁移能力降低,凋亡率升高(均P<0.05或P<0.01)。双荧光素酶报告基因和实验证实BIN1是miR-28-3p的靶基因,miR-28-3p抑制剂可上调MDA-MB-468细胞中BIN1蛋白的表达(P<0.05)。结论:miR-28-3p在TNBC组织及细胞中呈高表达状态,mi R-28-3p抑制剂上调BIN1表达进而抑制MDA-MB-468细胞的增殖、迁移和侵袭能力,并促进其凋亡。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.
