The identify role and molecular mechanism of the MALAT1/hsa-mir-20b-5p/TXNIP axis in liver inflammation caused by CHB in patients with chronic HBV infection complicated with NAFLD

Virus Res. 2021 Jun:298:198405. doi: 10.1016/j.virusres.2021.198405. Epub 2021 Mar 26.

Abstract

Background/aims: To identify the inflammatory damage caused by chronic hepatitis B (CHB) in patients of chronic hepatitis B virus (HBV) infection complicated with non-alcoholic fatty liver disease (NAFLD), then guiding clinicians to carry out antiviral treatment.

Methods: According to the pathological features of liver biopsy, treatment-naïve obese patients of chronic HBV infection complicated with NAFLD who had elevated alanine transaminase (ALT) were divided into CHB group and NASH group. Transcriptome chips were used to analyze the expression profiles of long non-coding RNA (lncRNA) and mRNA in liver puncture tissues from the two groups. The chip data of CHB and NASH groups were analyzed for differential expression analysis, gene function analysis, signal pathway analysis, target gene prediction and competing endogenous RNAs (ceRNA) network analysis.

Results: By comparing CHB group with NASH group, a total of 44 differentially expressed lncRNAs and 567 differentially expressed mRNAs were screened. GO analysis predicted that the differentially expressed mRNAs may affect monooxygenase activity and oxidoreductase activity. KEGG analysis predicted that the differentially expressed mRNAs may be related to signaling pathways involved in oxidative phosphorylation, phagosomes, and NAFLD. Differential analysis of lncRNA shown that the expression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in CHB group was significantly upregulated. Subsequently, through target gene prediction and ceRNA network analysis, we found thioredoxin interacting protein (TXNIP), which was significantly upregulated in the CHB group and had a ceRNA relationship with MALAT1. It is predicted that there may be a ceRNA regulation relationship of MALAT1/hsa-miR- 20b-5p/TXNIP.

Conclusion: The MALAT1/hsa-miR-20b-5p/TXNIP axis may mediate CHB-induced inflammatory damage in chronic HBV infection complicated with NAFLD, and the mechanism may be related to the activation of NLRP3 inflammatory bodies and downstream inflammatory responses.

Keywords: Chronic hepatitis B; Long non-coding RNA; Lung adenocarcinoma transcript 1; Non-alcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins* / genetics
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / genetics
  • Humans
  • Inflammation
  • MicroRNAs* / genetics
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Non-alcoholic Fatty Liver Disease* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger / genetics

Substances

  • Carrier Proteins
  • MALAT1 long non-coding RNA, human
  • MIRN20b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • TXNIP protein, human