LncRNA AC040162.3 Promotes HCV-Induced T2DM Deterioration Through the MiRNA-223-3p/NLRP3 Molecular Axis

Overview

Journal Anal Cell Pathol (Amst)

Specialties Cell Biology
Oncology
Pathology

Date 2023 Jun 26

PMID 37359091

Authors

Ben Niu

Xueshan Xia

Lijing Ma

Lixuan Yao

Yating Zhang

Heng Su

Affiliations

Soon will be listed here.

Abstract

Background: Diabetes is one of the most common diseases and major public health burdens worldwide. Type 2 diabetes mellitus (T2DM) is associated with chronic hepatitis C virus (HCV) infection, and lncRNAs play an important role in HCV-induced T2DM. We aimed to explore the effect of lncRNA AC040162.3 on HCV-induced T2DM.

Methods: HCV was used to infect MIN6 cells to establish an in vitro model. HCV copy number and miRNA expression were detected by Real Time Quantitative PCR (RT-qPCR). Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect the secretion of insulin, and methyl thiazolyl tetrazolium (MTT) was applied to analyze cell viability. Apoptosis was analyzed by Western blotting and flow cytometry. In addition, Western blotting and TdT-mediated dUTP Nick End Labeling (TUNEL) were used to analyze pyroptosis. Luciferase reporter assays were used to investigate the targeting relationship.

Results: The expression of LncRNA AC040162.3 and NLRP3 was markedly increased in HCV-T2DM, while the expression of miR-223-3p was remarkably inhibited. In vitro experiments demonstrated that lncRNA AC040162.3 silencing or miR-223-3p overexpression remarkably alleviated HCV-induced T2DM deterioration by inhibiting cell apoptosis and pyroptosis and enhancing cell viability. We then demonstrated that silencing lncRNA AC040162.3 promoted the expression of miR-223-3p and that miR-223-3p bound to lncRNA AC040162.3 and the NLRP3 binding site. In addition, the protective effects of LncRNA AC040162.3 silencing in HCV-infected MIN6 cells were reversed by overexpression of NLRP3 or silencing of miR-223-3p.

Conclusion: Silencing of lncRNA AC040162.3 alleviates the process of HCV-induced T2DM by governing the miR-223-3p/NLRP3 axis.

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