MiR-27a/b Regulates Liver Regeneration by Posttranscriptional Modification of Tmub1.

Abstract

Transmembrane and ubiquitin-like domain-containing 1 protein (Tmub1) negatively regulates liver regeneration. However, whether this regulation involves posttranscriptional modification of Tmub1 expression is unknown. The aim of the study was to investigate whether microRNA (miR)-27a/b regulates posttranscriptional modification of Tmub1 and cell proliferation during liver regeneration. Tmub1 mRNA 3'-untranslated region (UTR) sequences were analyzed using online software. A luciferase assay was used to verify the relationship between miR-27a/b and the 3'-UTR of Tmub1. Rat partial hepatectomy models were used to investigate miR-27a/b and Tmub1 levels after partial hepatectomy. MiR-27a/b expression was down- and up-regulated with mimics and inhibitors, respectively, to observe the effects of miR-27a/b on Tmub1 expression. Quantitative RT-PCR and Western blot analyses were used to measure miR-27a/b and Tmub1 expression. Hepatocyte proliferation was measured using the CCK8 method for BRL-3A liver cells and proliferating cell nuclear antigen and histone H3 phosphorylation in the regenerating liver. A potential binding site of miR-27a/b was found in the 3'-UTR sequence of Tmub1. Our luciferase assay confirmed that the Tmub1 mRNA 3'-UTR was the target of miR-27a/b. We observed a temporal correlation between miR-27a/b and Tmub1 expression during liver regeneration. MiR-27a/b down-regulated Tmub1 expression both in vivo and in vitro. MiR-27a/b regulated hepatocyte proliferation during liver regeneration. MiR-27a/b regulates hepatocyte proliferation by controlling posttranscriptional modification of Tmub1 during liver regeneration.