Silencing of lncRNA SNHG20 delays the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma via regulating liver Kupffer cells polarization.

Abstract

This study aims to investigate the role of long noncoding RNA SNHG20 in the progression of nonalcoholic fatty liver disease (NALFD) to hepatocellular carcinoma (HCC), and to elucidate whether polarization of Kupffer cells (KCs, liver macrophages) was involved in this process. Mouse NALFD was induced by 16 weeks of high-fat diet (HFD) feeding. Mouse NALFD-HCC was induced by 36 weeks of HFD feeding (from 1 week to 36 weeks) and 20 weeks of diethyl nitrosamine (DEN) administration (from 17 weeks to 36 weeks). The LV-shRNA- and LV-sh-SNHG20-infected RAW264.7 cells were injected into the NALFD mice followed by DEN treatment to evaluate the role of SNHG20 in regulating the progression of NALFD to HCC in mice. The proportion of M1 and M2 macrophages was determined by flow cytometry. The levels of M1-related inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α and M2-related Arg-1 and interleukin (IL)-10 were also examined. SNHG20 expression was decreased in NALFD but increased in NALFD-HCC, both in human and experimental mouse livers. Furthermore, human and mouse NALFD-HCC KCs displayed decreased M1/M2 ratio compared with NALFD KCs. Moreover, SNHG20 overexpression induced M2 polarization through activating STAT6, whereas SNHG20 silencing suppressed M1 polarization in RAW264.7 macrophages and delayed the progression of NALFD to HCC in mice. SNHG20 may facilitate the progression of NALFD to HCC via inducing liver KCs M2 polarization via STAT6 activation.