H19 potentiates let-7 family expression through reducing PTBP1 binding to their precursors in cholestasis.

摘要: Cholestasis induces the hepatic long non-coding RNA H19, which promotes progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed qPCR validation, we identified marked upregulation eight members let-7 family in livers bile duct ligation (BDL) and overexpression. In particular, expression let-7a-1/7d/7f-1 was highly induced H19-BDL but decreased H19KO-BDL livers. Interestingly, nuclear precursors as well primary transcripts levels BDL mouse Bioinformatics, pull-down, immunoprecipitation (RIP) assays revealed crucial RNA-binding protein polypyrimidine tract-binding 1 (PTBP1), an interaction partner, interacted with let-7a-1 let-7d suppressed their maturation. Both PTBP1 differentially regulated different acid species hepatocyte cholangiocyte cells. Further, negatively PTBP1’s mRNA did not affect its subcellular distribution Moreover, found restrained facilitated bioavailability miRNAs to targets. Taken together, this study for first time promoted decreasing level binding cholestasis.