Partial hepatectomy‑induced upregulation of SNHG12 promotes hepatocyte proliferation and liver regeneration

Mol Med Rep. 2020 Mar;21(3):1089-1096. doi: 10.3892/mmr.2019.10904. Epub 2019 Dec 27.

Abstract

Following partial hepatectomy (PH), the complex process of liver regeneration is initiated, which encompasses the synchronized induction of hepatocyte proliferation. Hepatocyte proliferation can be regulated by multiple stimuli, including long non‑coding RNAs (lncRNAs) and Wnt/β‑catenin signaling, although the underlying mechanism of lncRNA/Wnt in liver regeneration remains unclear. In the present study, a liver regeneration‑associated functional lncRNA was identified, and its function was delineated in vitro and in vivo; lncRNA small nucleolar RNA host gene 12 (SNHG12) was revealed to be upregulated at various time‑points after 2/3 PH. The expression of SNHG12 was also increased in normal liver cell lines treated with different concentrations of hepatocyte growth factor (HGF). Functionally, SNHG12 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio of SNHG12‑overexpressing mice was significantly higher than that of the control mice. Overexpression of SNHG12 promoted the activation of Wnt/β‑catenin signaling in hepatocytes. Furthermore, specific inhibition of Wnt/β‑catenin signaling significantly attenuated SNHG12‑induced hepatocyte proliferation and the affected liver/body weight ratio. Collectively, the results of the present study indicated that SNHG12 contributes to liver regeneration by activating Wnt/β‑catenin signaling. Therefore, drugs that regulate the SNHG12/Wnt axis may be beneficial for liver regeneration following PH.

Keywords: long non-coding rna; small nucleolar rna host gene 12; Wnt/β-catenin; liver regeneration; partial hepatectomy.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Culture Techniques
  • Cell Proliferation
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • Hepatectomy*
  • Hepatocytes / metabolism*
  • Immunohistochemistry
  • Liver Regeneration / genetics*
  • Male
  • Mice
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Wnt Signaling Pathway

Substances

  • Biomarkers
  • RNA, Long Noncoding