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
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:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD mo...Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.展开更多
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.
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 Natural Science Foundation of China[grant numbers 81630018,82070538,,81870374]Guangdong Science and Technology Department[grant number 2017A030306021]Guangzhou Science and Technology Department[grant number 202002030041].
文摘Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.
