Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease.

ABSTRACT:

Background & aims

Polycystic liver disease (PLD) is characterised by increased autophagy and reduced miRNA levels in cholangiocytes. Given that autophagy has been implicated in miRNA regulation, we tested the hypothesis that increased autophagy accounts for miRNA reduction in PLD cholangiocytes (PLDCs) and accelerated hepatic cystogenesis.

Methods

We assessed miRNA levels in cultured normal human cholangiocytes (NHCs), PLDCs, and isolated PLDC autophagosomes by miRNA-sequencing (miRNA-seq), and miRNA targets by mRNA-seq. Levels of miR-345 and miR-345-targeted proteins in livers of animals and humans with PLD, in NHCs and PLDCs, and in PLDCs transfected with pre-miR-345 were assessed by in situ hybridisation (ISH), quantitative PCR, western blotting, and fluorescence c

SUBMITTER: Masyuk T 

PROVIDER: S-EPMC8449272 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature