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
BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ...BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ferroptosis and its impact on diabetes-induced myocardial infarction via the PI3K/AKT/GSK3βpathway.METHODS We constructed bones mesenchymal stem cells(BMCs)with low miR-142-3p expression and investigated its role using cell flow cytometry and western blotting(WB).A diabetes myocardial infarction model was established using streptozotocin and coronary artery ligation.The rats were divided into six groups(n=15 per group):Control,sham surgery model,liraglutide intervention,BMCs intervention,and low miR-142-3p BMCs intervention.Interventions lasted for 7 days and BMCs injected for once.Blood glucose levels were monitored,and myocardial infarction improvements were assessed via electrocardiogra,general heart observation,staining techniques,and WB analysis.RESULTS We observed that miR-142-3p increased BMC apoptosis and affected AKT and GSK3β.The myocardial infarction drug,liraglutide,BMCs,and miR-142-3p low expression BMCs intervention showed improvement in differing degrees.The liraglutide and BMCs showed significant blood glucose reduction(0.05).BMCs increased the expression of PI3K,AKT,and GSK3,leading to an increase in the myocardial infarction intervention group,liraglutide,and BMCs intervention groups.The low miR-142-3p expression intervention with BMCs group had the lowest PI3K and AKT protein expression.Liraglutide improved ferroptosis markers(increased COX-2,decreased GPX4 and CHCHD6).Low miR-142-3p BMCs increased COX-2,GPX4,and CHCHD6.CCM3 and VEGFR2 expression increased in BMCs and low miR-142-3p groups,promoting myocardial repair,but decreased in the low miR-142-3p groups.CONCLUSION The preliminary results showed that the therapeutic mechanism of BMCs in diabetes myocardial infarction may involve miR-142-3p via the PI3K/AKT/GSK-3βaxis,which jointly inhibits ferroptosis and programmed death.展开更多
Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long...Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies.Studies have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be characterized.Therefore,our study aimed to explore the role and underlying mechanism of SNHG4 in GC.Methods:We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells.Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients.Cellular function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and invasion.We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth.Mechanically,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC patients.SNHG4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro.The in vivo experiment indicated that SNHG4 facilitated GC tumor growth.Furthermore,SNHG4 was demonstrated to bind to miR-409-3p.Moreover,CREB1 was directly targeted by miR-409-3p.Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy.Additionally,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1.Conclusion:In conclusion,we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1,which may deepen the understanding of the underlying mechanism in GC development.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 Health Commission Project,No.Z2014334Natural Science Foundation of Guangxi Province,China,No.2020GXNSFAA238036.
文摘BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ferroptosis and its impact on diabetes-induced myocardial infarction via the PI3K/AKT/GSK3βpathway.METHODS We constructed bones mesenchymal stem cells(BMCs)with low miR-142-3p expression and investigated its role using cell flow cytometry and western blotting(WB).A diabetes myocardial infarction model was established using streptozotocin and coronary artery ligation.The rats were divided into six groups(n=15 per group):Control,sham surgery model,liraglutide intervention,BMCs intervention,and low miR-142-3p BMCs intervention.Interventions lasted for 7 days and BMCs injected for once.Blood glucose levels were monitored,and myocardial infarction improvements were assessed via electrocardiogra,general heart observation,staining techniques,and WB analysis.RESULTS We observed that miR-142-3p increased BMC apoptosis and affected AKT and GSK3β.The myocardial infarction drug,liraglutide,BMCs,and miR-142-3p low expression BMCs intervention showed improvement in differing degrees.The liraglutide and BMCs showed significant blood glucose reduction(0.05).BMCs increased the expression of PI3K,AKT,and GSK3,leading to an increase in the myocardial infarction intervention group,liraglutide,and BMCs intervention groups.The low miR-142-3p expression intervention with BMCs group had the lowest PI3K and AKT protein expression.Liraglutide improved ferroptosis markers(increased COX-2,decreased GPX4 and CHCHD6).Low miR-142-3p BMCs increased COX-2,GPX4,and CHCHD6.CCM3 and VEGFR2 expression increased in BMCs and low miR-142-3p groups,promoting myocardial repair,but decreased in the low miR-142-3p groups.CONCLUSION The preliminary results showed that the therapeutic mechanism of BMCs in diabetes myocardial infarction may involve miR-142-3p via the PI3K/AKT/GSK-3βaxis,which jointly inhibits ferroptosis and programmed death.
文摘Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies.Studies have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be characterized.Therefore,our study aimed to explore the role and underlying mechanism of SNHG4 in GC.Methods:We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells.Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients.Cellular function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and invasion.We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth.Mechanically,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC patients.SNHG4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro.The in vivo experiment indicated that SNHG4 facilitated GC tumor growth.Furthermore,SNHG4 was demonstrated to bind to miR-409-3p.Moreover,CREB1 was directly targeted by miR-409-3p.Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy.Additionally,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1.Conclusion:In conclusion,we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1,which may deepen the understanding of the underlying mechanism in GC development.
