Long Noncoding RNA X-inactive Specific Transcript (lncRNA XIST) Inhibits Hepatic Insulin Resistance by Competitively Binding MicroRNA-182-5p

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2023 Nov 29

PMID 38018594

Authors

Guoqing Zhong

Qingping Yang

Yihua Wang

Yuan Liang

Xiaojing Wang

Dongli Zhao

Affiliations

Soon will be listed here.

Abstract

Background: What is highlighted in this study refers to the role and molecular mechanism of long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) in cells with insulin resistance (IR).

Methods: In this study, LX-2 cells were applied to establish IR model in vitro. The expressions of lncRNA XIST, phosphoenolpyruvate carboxykinase (PEPCK,) and glucose-6-phosphatase (G6Pase) were quantified by quantitative reverse transcription polymerase chain reaction. The 2-deoxy-d-glucose-6-phosphate (2-DG6P) level was detected utilizing 2-deoxy-d-glucose (2-DG) uptake measurement kit. Western blot was adopted to measure the protein expressions of insulin-like growth factor-1 receptor (IGF-1R), G6Pase, PEPCK, and phosphatidylinositol 3-kinase (PI3K)/Akt pathway-related genes. StarBase was used to predict the targeting relationship between lncRNA XIST or IGF-1R with miR-182-5p, the results of which were verified by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Rescue experiments were conducted to investigate the effect of miR-182-5p on IR cells. Next, low-expressed lncRNA XIST and high-expressed miR-182-5p were observed in IR cells.

Results: Upregulation of lncRNA XIST increased IGF-1R and 2-DG6P levels, decreased G6Pase and PEPCK expressions, and promoted PI3K/Akt pathway activation in IR cells. LncRNA XIST sponged miR-182-5p which targeted IGF-1R. MiR-182-5p mimic reversed the above effects of lncRNA XIST overexpression on IR cells.

Conclusions: In conclusion, lncRNA XIST/miR-182-5p axis alleviates hepatic IR in vitro via IGF-1R/PI3K/Akt signaling pathway, which could be the promising therapeutic target.

Citing Articles

Long noncoding RNA X-inactive specific transcript (lncRNA XIST) inhibits hepatic insulin resistance by competitively binding microRNA-182-5p.

Zhong G, Yang Q, Wang Y, Liang Y, Wang X, Zhao D Immun Inflamm Dis. 2023; 11(11):e969.

PMID: 38018594 PMC: 10629262. DOI: 10.1002/iid3.969.

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