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
  • 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. [email protected].
  • 6. Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. [email protected].
  • 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. [email protected].
  • 8. Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China. [email protected].
  • # 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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