目的:探究微小RNA(miR)-574-3p、序列相似家族3成员C(family with sequence similarity 3 member C,FAM3C)在食管癌组织中的表达,并分析二者与患者临床病理特征的关系。方法:选取2018年5月至2020年5月于本院行手术治疗的90例食管癌患者...目的:探究微小RNA(miR)-574-3p、序列相似家族3成员C(family with sequence similarity 3 member C,FAM3C)在食管癌组织中的表达,并分析二者与患者临床病理特征的关系。方法:选取2018年5月至2020年5月于本院行手术治疗的90例食管癌患者,收集术中留取的癌组织和癌旁组织标本。使用qRT-PCR法检测组织中miR-574-3p、FAM3C mRNA相对表达量;使用免疫组织化学法检测组织中FAM3C蛋白表达情况;采用Spearman等级相关分析食管癌组织中miR-574-3p、FAM3C的相关性;Kaplan-Meier法分析miR-574-3p、FAM3C与预后的关系。结果:食管癌患者癌组织中miR-574-3p低表达,FAM3C mRNA、FAM3C蛋白高表达(P<0.05)。食管癌组织中miR-574-3p、FAM3C蛋白表达水平具有负相关性(r=-0.420,P<0.05)。Pearson相关性分析显示,食管癌组织中miR-574-3p、FAM3C mRNA表达具有负相关性(r=-0.731,P<0.05)。miR-574-3p、FAM3C蛋白均与TNM分期、浸润程度、淋巴结转移有关(P<0.05)。miR-574-3p高表达组3年累积生存率为83.72%,显著高于miR-574-3p低表达组(53.19%);FAM3C高表达组3年累积生存率为56.86%,显著低于FAM3C低表达组(82.05%),差异均有统计学意义(log rankχ^(2)=10.175、7.290,P<0.05)。结论:食管癌组织中miR-574-3p表达水平较低,FAM3C表达水平较高,且二者具有负相关性,与临床病理特征中的TNM分期、浸润程度、淋巴结转移以及患者3年累积生存率有关。展开更多
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
Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the...Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.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Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.
