Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury.
Exp Mol Med
; 54(11): 2022-2035, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-36424455
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-3ß/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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1
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
ARN Largo no Codificante
Idioma:
En
Revista:
Exp Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2022
Tipo del documento:
Article