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

作者全名："Chen, Xuanxin; Zhou, Shibo; Chen, Yiyu; Tong, Kexin; Huang, Wenxiang"

作者地址："[Chen, Xuanxin; Tong, Kexin; Huang, Wenxiang] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing 400016, Peoples R China; [Zhou, Shibo] Chongqing Univ Technol, Coll Mat Sci & Engn, Chongqing 400054, Peoples R China; [Chen, Yiyu] Chongqing Med Univ, Stomatol Hosp, Dept Clin Lab, Chongqing 401120, Peoples R China"

通信作者："Huang, WX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing 400016, Peoples R China."

来源：CLINICAL NUTRITION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001126196400001

JCR分区：Q1

影响因子：6.3

年份：2024

卷号：43

期号：1

开始页：52

结束页：64

文献类型：Article

关键词：MIR22HG; NASH; Autophagy; Pyroptosis; Fibrosis

摘要："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.(c) 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved."

基金机构：Chongqing Yuzhong Science and Technology Commission [20200119]

基金资助正文：<B>Funding</B> This work received support from Chongqing Science and Tech-nology Bureau (Project No. : CSTB2022NSCQ-MSX0 092) andr Chongqing Yuzhong Science and Technology Commission (20200119) . All data generated or analyzed in this study are avail-able from the corresponding author for reasonable request.