The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration

Li,Cuicui; Chang,Lei; Chen,Zhiquan; Liu,Zhongzhong; Wang,Yanfeng; Ye,Qifa

doi:10.3892/ijmm.2017.2854

The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration

Authors:
- Cuicui Li
- Lei Chang
- Zhiquan Chen
- Zhongzhong Liu
- Yanfeng Wang
- Qifa Ye
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Affiliations: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China, Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: January 11, 2017 https://doi.org/10.3892/ijmm.2017.2854
Pages: 347-356
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice. We explored the functions of lncRNA MALAT1 with a series of functional analyses in vitro. We found that MALAT1 was upregulated during liver regeneration. Moreover, MALAT1 accelerated hepatocyte proliferation by stimulating cell cycle progression from the G1 to the S phase and inhibiting apoptosis in vitro. In addition, our findings also demonstrated that MALAT1 was regulated by p53 during liver regeneration, and that p53 may be a key upstream regulator of MALAT1 activity. Mechanistically, we found that MALAT1 activated the Wnt/β‑catenin pathway by inhibiting the expression of Axin1 and adenomatous polyposis coli (APC), and subsequently promoting the expression of cyclin D1. On the whole, the findings of this study suggest that MALAT1 is a critical molecule for liver regeneration. Pharmacological interventions targeting MALAT1 may thus prove to be therapeutically beneficial in liver failure or liver transplantation by promoting liver regeneration.

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