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
Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2...Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.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.
基金supported by the National Key Research and Development Program of China(2022YFD1300303,2021YFF1000602)National Natural Science Foundation of China(32472878)China Agriculture Research System(CARS-35-PIG)。
文摘Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.
