LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis

Xuanxin Chen; Shibo Zhou; Yiyu Chen; Kexin Tong; Wenxiang Huang

doi:10.1016/j.clnu.2023.11.004

LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis

Clin Nutr. 2024 Jan;43(1):52-64. doi: 10.1016/j.clnu.2023.11.004. Epub 2023 Nov 22.

Authors

Xuanxin Chen¹, Shibo Zhou², Yiyu Chen³, Kexin Tong¹, Wenxiang Huang⁴

Affiliations

¹ Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
² College of Materials Science and Enginering, Chongqing University of Technology, Chongqing 400054, China.
³ Department of Clinical Laboratory, Stomatological Hospital of Chongqing Medical University, Chongqing 401120, China.
⁴ Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: wenxlang_huang@163.com.

PMID: 38011754
DOI: 10.1016/j.clnu.2023.11.004

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is known to progress due to the impact of long non-coding RNAs (lncRNAs), which have been linked to autophagy, pyroptosis, and fibrosis in NASH cells. However, the exact mechanisms underpinning these processes remain unclear. This study focuses on the role of lncRNA MIR22HG (MIR22HG) in NASH.

Methods: The expression of differentially expressed lncRNA was analyzed by RNA sequencing. Mouse models of NASH induced by MCD and HFD were validated. The expression of MIR22HG in HFD and MCD mouse liver tissue samples, FFA cells constructed with HepG2 and Huh7, and human liver tissue samples were detected by QRT-PCR. In addition, We used RNA immunoprecipitation, luciferase reporting, miRNA transfection, plasmid construction, immunofluorescence, Western blot, qRT-PCR, ELISA, and hybridization techniques to elucidate the relationship between MIR22HG, microRNA-9-3p (miR-9-3p), and IGF1. In addition, the mechanism of MIR22HG and PTEN/AKT was explored by Western blot analysis.

Results: RNA-seq found that 3751 mRNAs and 23 lncRNAs were differentially expressed, which constituted a lncRNA-miRNA-mRNA regulatory network. Studies demonstrated the downregulation of MIR22HG in HFD and MCD mouse liver tissue samples (p = 1.00E-04 and p = 4.6E-03). Our results showed that overexpression of MIR22HG promoted autophagy and inhibited pyroptosis and fibrosis through the miR-9-3p/IGF1 pathway, thus slowing the occurrence and development of NASH. Further, we observed a low expression of MIR22HG and IGF1, but a high expression of miR-9-3p in NASH patients, a finding in alignment with our in vivo and in vitro results.

Conclusion: Using MIR22HG as a biomarker and therapeutic target for NASH patients, we found that it plays a pivotal role in detecting autophagy, pyroptosis, and fibrosis through the ceRNA pathway.

Keywords: Autophagy; Fibrosis; MIR22HG; NASH; Pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / genetics
Fibrosis
Humans
Insulin-Like Growth Factor I / metabolism
Mice
MicroRNAs* / genetics
Non-alcoholic Fatty Liver Disease* / genetics
Pyroptosis
RNA, Competitive Endogenous
RNA, Long Noncoding* / genetics

Substances

IGF1 protein, human
Insulin-Like Growth Factor I
MicroRNAs
RNA, Competitive Endogenous
RNA, Long Noncoding
MIRN22 microRNA, human
MIRN9 microRNA, human