2. Academic Validation
  3. Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury

Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury

  • Exp Mol Med. 2022 Nov 24. doi: 10.1038/s12276-022-00881-2.
Zhenjun Yu # 1 2,  Yuhan Li # 1,  Shuai Shao # 2,  Beichen Guo 1,  Mengxia Zhang 3,  Lina Zheng 3,  Kun Zhang 3,  Feng Zhou 1,  Li Zhang 4,  Chiyi Chen 4,  Wentao Jiang 5,  Wei Hong 6,  Tao Han 7 8
Affiliations

Affiliations

  • 1 Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 2 Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China.
  • 3 Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 4 Liver transplant department, Organ transplant center, Tianjin First Center Hospital, Tianjin, China.
  • 5 Liver transplant department, Organ transplant center, Tianjin First Center Hospital, Tianjin, China. jiangwentao@vip.163.com.
  • 6 Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. hongwei@tmu.edu.cn.
  • 7 Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University; Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. hantaomd@126.com.
  • 8 Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China. hantaomd@126.com.
  • # Contributed equally.
PMID: 36424455 DOI: 10.1038/s12276-022-00881-2
Abstract

Some long noncoding RNAs (lncRNAs), which harbor MicroRNAs in their gene sequence and are also known as MicroRNA host gene derived lncRNAs (lnc-MIRHGs), play a dominant role alongside miRNAs, or both perform biological functions synergistically or independently. However, only a small number of lnc-MIRHGs have been identified. Here, multiple liver injury datasets were analyzed to screen and identify the target lncRNA Mir122hg. Mir122hg was mainly enriched in liver tissues with human-mouse homology. In both CCl4-induced acute liver injury and Dgal/LPS-induced fulminant liver failure in mice, Mir122hg was sharply downregulated at the early stage, while a subsequent significant increase was only found in the CCl4 group with liver recovery. Overexpression and silencing assays confirmed that Mir122hg played a protective role in acute injury by promoting hepatocyte proliferation in vivo and in vitro. Consistent with the results of gene enrichment analysis, Mir122hg binding to C/EBPα affected its transcriptional repression, promoted gene transcription of downstream chemokines, Cxcl2, Cxcl3, and Cxcl5, and exerted pro-proliferative effects on hepatocytes through activation of the Akt/GSK-3β/p27 signaling pathway by CXC/CXCR2 complexes. This study identifies a novel lncRNA with protective effects in acute liver injury and demonstrates that the binding of Mir122hg-C/EBPα promotes hepatocyte proliferation via upregulation of CXC chemokine and activation of Akt signaling.

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