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
文摘目的 探讨微小RNA(miR)-152和miR-22-3p在妊娠期糖尿病(GDM)患者外周血中的表达及意义。方法 选取2018年3月—2023年3月杭州市第九人民医院收治的96例GDM患者作为实验组,另选取健康孕妇96例作为对照组。采用qRT-PCR法检测两组孕妇血清miR-152和miR-22-3p水平及孕妇临床指标并进行比较,采用pearson法分析血清miR-152和miR-22-3p水平与临床指标相关性;Target Scan Human网站分别预测miR-152、miR-22-3p与细胞因子信号传导抑制因子3(SOCS3)的靶向关系,logistic回归分析孕妇发生GDM的影响因素;ROC曲线分析血清miR-152和miR-22-3p对孕妇是否发生GDM的预测价值。结果 GDM患者血清miR-152(1.03±0.25)和miR-22-3p(0.81±0.24)表达显著低于健康孕妇的(1.25±0.27)和(1.06±0.28),差异有统计学意义(P<0.05)。GDM患者FPG、2 h PG、FINS、TG、HbA1c、LDL-C、SOCS3、VCAM-1和HOMA-IR水平高于健康孕妇,HDL-C水平明显低于健康孕妇,差异均有统计学意义(P<0.05)。pearson分析结果表明,血清miR-152和miR-22-3p水平呈正相关(r=0.318,P<0.01),血清miR-152和miR-22-3p水平与FPG、2 h PG、FINS、TG、HbA1c、LDL-C、SOCS3、VCAM-1和HOMA-IR水平呈负相关(P<0.05)。Target Scan Human网站预测结果表明,miR-152和miR-22-3p均与SOCS3存在靶向结合位点;logistic分析结果显示miR-152、miR-22-3p、FPG、2 h PG、SOCS3、FINS、HbA1c、TG和VCAM-1均为孕妇发生GDM的影响因素(P<0.05)。ROC曲线结果表明,miR-152和miR-22-3p联合评估孕妇是否发生GDM的AUC(0.818)优于单一指标(P<0.05)。结论 GDM患者血清miR-152和miR-22-3p水平较低,两者均为孕妇发生GDM的影响因素。
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.
