Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor...Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stem展开更多
INTRODUCTION Congenital megaprepuce （CMP） is considered as a congenital penile malformation, which includes phimosis and severe ballooning of the redundant inner prepuce, conferring the typical aspect of concealed p...INTRODUCTION Congenital megaprepuce （CMP） is considered as a congenital penile malformation, which includes phimosis and severe ballooning of the redundant inner prepuce, conferring the typical aspect of concealed penis, in which the whole attachment is hidden within subcutaneous tissue.展开更多
基金supported by The Special Research Foundation of the National Nature Science Foundation of China (81972262,81972255,81801719,81772597)The Guangdong Basic and Applied Basic Research Foundation (2020A1515010117,2018A030313645,2016A030313840)+4 种基金the Fundamental Research Funds for the Central Universities (18ykpy22)Grant [2013]163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information TechnologyGrant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education InstitutesGrant from Guangdong Science and Technology Department (2015B050501004,2017B030314026)Grant from Sun Yat-sen University Clinical Research 5010 Program (2018008).
文摘Background and Aims:Patients with persistent positive hepatitis B surface antigen(HBsAg),even with a low HBVDNA load,have a higher risk of hepatocellular carcinoma(HCC)than those without HBV infection.Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms,this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA,and to explore underlying mechanisms.Methods:We screened out miR-203a,the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.In vitro and in vivo functional experiments were performed to assess its regulatory function.The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study.Results:MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis.The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells.We demonstrated the function of miR-203a in inhibiting HCC cell proliferation,migration,clonogenic capacity,and tumor development in vivo.Furthermore,the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers.In concordance with our study,the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a.We also found that BMI1,a gene maintains the self-renewal capacity of stem cells,showed a significant negative correlation with miR-203a in HCC specimen(p<0.001).Similarly,opposite BMI1 changes after overexpression/knockdown of miR203a were also confirmed in vitro.Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding.Conclusions:HBsAg may promote the development of HCC and tumor stem
文摘INTRODUCTION Congenital megaprepuce （CMP） is considered as a congenital penile malformation, which includes phimosis and severe ballooning of the redundant inner prepuce, conferring the typical aspect of concealed penis, in which the whole attachment is hidden within subcutaneous tissue.
