DNA Methylation Regulatory Axis miR-29b-3p/DNMT3B Regulates Liver Regeneration Process by Altering LATS1

Abstract

DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Hippo signalling pathway is a key signalling regulatory network in the growth and development of tissues and organs. Nevertheless, the precise role of DNA methylation and Hippo signalling pathway during liver regeneration (PH) is still unclear. In this study, we investigated the regulatory mechanism of LATS1, a pivotal protein in the Hippo signalling pathway, on liver regeneration and explored the specific mechanism of DNA methylation regulating LATS1. To analyse the regulation of LATS1 by DNA methylation, following 2/3 partial hepatectomy (PH) in liver-specific AAV-8 shDNMT3B deleted mice (DNMT3B, KD) mice and sex-matched AAV-8 shControl (Control). We determined that DNMT3B regulates the protein expression of LATS1 by DNA methylation. miR-29b-3p significantly regulates the expression of DNMT3B and alters LATS1 expression to inactivate the Hippo signalling pathway, thereby reducing the expression of cell proliferation and cycle proteins and inhibiting liver regeneration. Our results indicated that the miR-29b-3p/DNMT3B regulatory axis influences LATS1 expression through DNA methylation, and thereby promotes liver regeneration.