BACKGROUND The high mortality rate of hepatocellular carcinoma(HCC)in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection(HCV)and late diagnosis of the carcinoma.MicroRNAs(miRNA),which regu...BACKGROUND The high mortality rate of hepatocellular carcinoma(HCC)in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection(HCV)and late diagnosis of the carcinoma.MicroRNAs(miRNA),which regulate tumor proliferation and metastasis in HCC,may serve as a useful diagnostic approach for the early detection of HCC,thus decreasing its mortality.Meanwhile,endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes.AIM To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters.METHODS We compared levels of endocan and circulating miRNA 9-3p from 35 HCVrelated HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls recruited from inpatient and outpatient clinics of the National Liver Institute,Menoufia University,Egypt in the period from January to March 2021 in a case-control study.Serum samples from all groups were analyzed for HCV.Endocan was measured by enzymelinked immunosorbent assays,and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR.RESULTS The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease(P<0.001)and control(P<0.001)groups,while levels in the chronic liver disease were significantly lower than those in the control group(P<0.001).The levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease(P<0.001)and control(P<0.001)groups.Moreover miRNA 9-3p and endocan performed better thanα-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients.The levels of miRNA 9-3p were significantly inversely correlated to vascular invasion(P=0.002),stage of advancement of Barcelona Clinical Liver Cancer(P<0.001)and the metastatic site(P<0.001)of the HCC group.CONCLUSION Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.展开更多
OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demon...OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by mi R-124-3p in U87 and C6 glioblastoma cells.METHODS The functional inhibition of gap junctions using either si RNA or pharmacological inhibition eliminated the mi R-124-3p-mediated antiproliferation,whereas the enhancement of gap junctions with retinoic acid treatment augmented this mi R-124-3p-mediated antiproliferation.A similar effect was observed in glioblastoma xenograft models.RESULTS More importantly,patch clamp and co-culture assays demonstrated the transmission of mi R-124-3p through gap junction channels into adjacent cells.In further exploring the impact of gap junction-mediated transport of mi R-124-3p on mi R-124-3p target pathways,we found that mi R-124-3p inhibited glioblastoma cell growth in part by decreasing the protein expression of cyclindependent kinase 6,leading to cel cycle arrest at the G0/G1phase;moreover,pharmacological regulation of gap junctions affected this cell cycle arrest.CONCLUSION Our results indicate that the″bystander″effects of functional gap junctions composed of connexin 43 enhance the antitumor effect of mi R-124-3p in glioblastoma cells by transferring mi R-124-3p to adjacent cells,thereby enhancing G0/G1cell cycle arrest.These observations provide a new guiding strategy for the clinical application of mi RNA therapy in tumor treatment.展开更多
文摘BACKGROUND The high mortality rate of hepatocellular carcinoma(HCC)in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection(HCV)and late diagnosis of the carcinoma.MicroRNAs(miRNA),which regulate tumor proliferation and metastasis in HCC,may serve as a useful diagnostic approach for the early detection of HCC,thus decreasing its mortality.Meanwhile,endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes.AIM To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters.METHODS We compared levels of endocan and circulating miRNA 9-3p from 35 HCVrelated HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls recruited from inpatient and outpatient clinics of the National Liver Institute,Menoufia University,Egypt in the period from January to March 2021 in a case-control study.Serum samples from all groups were analyzed for HCV.Endocan was measured by enzymelinked immunosorbent assays,and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR.RESULTS The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease(P<0.001)and control(P<0.001)groups,while levels in the chronic liver disease were significantly lower than those in the control group(P<0.001).The levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease(P<0.001)and control(P<0.001)groups.Moreover miRNA 9-3p and endocan performed better thanα-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients.The levels of miRNA 9-3p were significantly inversely correlated to vascular invasion(P=0.002),stage of advancement of Barcelona Clinical Liver Cancer(P<0.001)and the metastatic site(P<0.001)of the HCC group.CONCLUSION Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.
基金The project supported by National Natural Science Foundation of China(81473234,U1303221)
文摘OBJECTIVE MicroR NA(miR NA)holds promise as a novel therapeutic tool for cancer treatment.However,the transfection efficiency of current delivery systems represents a bottleneck for clinical applications.Here,we demonstrate that gap junctions mediate an augmentative effect on the antiproliferation mediated by mi R-124-3p in U87 and C6 glioblastoma cells.METHODS The functional inhibition of gap junctions using either si RNA or pharmacological inhibition eliminated the mi R-124-3p-mediated antiproliferation,whereas the enhancement of gap junctions with retinoic acid treatment augmented this mi R-124-3p-mediated antiproliferation.A similar effect was observed in glioblastoma xenograft models.RESULTS More importantly,patch clamp and co-culture assays demonstrated the transmission of mi R-124-3p through gap junction channels into adjacent cells.In further exploring the impact of gap junction-mediated transport of mi R-124-3p on mi R-124-3p target pathways,we found that mi R-124-3p inhibited glioblastoma cell growth in part by decreasing the protein expression of cyclindependent kinase 6,leading to cel cycle arrest at the G0/G1phase;moreover,pharmacological regulation of gap junctions affected this cell cycle arrest.CONCLUSION Our results indicate that the″bystander″effects of functional gap junctions composed of connexin 43 enhance the antitumor effect of mi R-124-3p in glioblastoma cells by transferring mi R-124-3p to adjacent cells,thereby enhancing G0/G1cell cycle arrest.These observations provide a new guiding strategy for the clinical application of mi RNA therapy in tumor treatment.
