Knockdown of long noncoding RNA MIAT attenuates cigarette smoke-induced airway remodeling by downregulating miR-29c-3p–HIF3A axis. (1st March 2022)

• Record Type: Journal Article
• Authors: Gu, Wenchao; Wang, Linxuan; Deng, Guoping; Gu, Xiaolong; Tang, Zhijun; Li, Shanshan; Jin, Wenjing; Yang, Junxia; Guo, Xiaoxia; Li, Qiang
• Is Part Of: Toxicology letters. Volume 357(2022)
• Page Start: 11
• Page End: 19
• Publication Date: 2022-03-01
• Subjects: Chronic obstructive pulmonary disease -- MIAT -- Cigarette smoke -- Airway remodeling -- miR-29c-3p-HIF3A axis; COPD chronic obstructive pulmonary disease -- CS cigarette smoke -- MIAT myocardial-infarction–associated transcript -- EMT epithelial-mesenchymal transition -- HIF3A hypoxia-inducible factor 3 alpha -- BALF bronchoalveolar lavage fluid -- 3'UTR 3' untranslated region; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.12.014
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Knockdown of MIAT attenuates CS-induced airway remodeling in mice. MIAT knockdown reverses CSE-induced apoptosis, inflammation, and collagen deposition in bronchial epithelial cells. MIAT upregulates HIF3A via sponging of miR-29c-3p. Abstract: Chronic obstructive pulmonary disease (COPD) is a global public health issue and is defined as persistent airflow limitation. COPD is a major cause of morbidity and mortality worldwide. Long noncoding RNAs are involved in the course of pulmonary diseases. Here, we revealed that a long noncoding RNA called myocardial-infarction–associated transcript ( MIAT ) is upregulated in lung tissues of cigarette smoke (CS)-exposed mice. Knockdown of MIAT attenuated CS or CS-extract–induced inflammatory processes, epithelial-mesenchymal transition (EMT), and collagen deposition. Moreover, according to bioinformatic analyses and luciferase reporter assays, MIAT binds to microRNA-29c-3p (miR-29c-3p) and upregulates hypoxia-inducible factor 3 alpha ( HIF3A ), a target gene of miR-29c-3p. When the MIAT- specific short hairpin RNA and an miR-29c-3p inhibitor were cotransfected into cells, the inhibitor reversed the effects of MIAT knockdown on cell proliferation, apoptosis, inflammation, EMT, and collagen deposition. Overall, these results indicate that MIAT participates in CS-induced EMT and airway remodeling in COPD by upregulating miR-29c-3p–HIF3A axis output, thereby offering a novel promising biomarker for the assessment of COPD exacerbation induced by CS exposure.