LncRNA XIST facilitates hypoxia-induced myocardial cell injury through targeting miR-191-5p/TRAF3 axis

• Published in: Molecular and cellular biochemistry 2022-06, Vol.477 (6), p.1697-1707
• Main Authors: Wang, Yonghong, Liu, Yanfei, Fei, Aike, Yu, Zaixin
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Apoptosis - physiology; Assaying; BAX protein; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Cardiology; Cardiomyocytes; Cardiovascular diseases; Cell injury; Cell Proliferation; Cell viability; Cholecystokinin; Flow cytometry; Heart attack; Humans; Hypoxia; Hypoxia - metabolism; Injury prevention; Life Sciences; Medical Biochemistry; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Molecular interactions; Myocardial infarction; Myocytes, Cardiac - metabolism; Non-coding RNA; Oncology; Polymerase chain reaction; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; TNF Receptor-Associated Factor 3 - genetics; TNF Receptor-Associated Factor 3 - metabolism; Transcription; Tumor necrosis factor receptors
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-022-04385-5

Myocardial infarction is one of the most lethal diseases in cardiovascular diseases. In the present work, we aimed to elucidate the molecular and functional association long non-coding RNA (lncRNA) X-inactive specific transcript (XIST), microRNA (miR)-191-5p, and TNF receptor-associated factor 3 (TRAF3). Human cardiomyocyte primary cells (HCMs) were stimulated by hypoxia to establish a model of myocardial injury in vitro. The relative expressions of XIST, miR-191-5p, and TRAF3 were measured using quantitative real-time polymerase chain reaction (qRT-PCR) assay. The capabilities of proliferation and apoptosis were determined using cell counting kit (CCK-8) and flow cytometry assays, respectively. The molecular interactions were verified using dual luciferase assay. The protein contents of TRAF3, Bcl-2, and Bax were calculated using western blot assay. XIST was significantly increased, but miR-191-5p was reduced in hypoxia-treated HCMs compared to that in control group. Either downregulated XIST or enforced miR-191-5p markedly enhanced cell viability and restrained cell apoptotic rate in hypoxia-treated HCMs. Mechanistically, XIST directly interacted with miR-191-5p to competitive releasing TRAF3 expression. Importantly, overexpression of TRAF3 dramatically diminished the protective effects of XIST knockdown on hypoxia-triggered HCMs injury. Collectively, our data elucidated a novel “lncRNA XIST/miR-191-5p/TRAF3” molecular network in vitro, indicating that the reduced lncRNA XIST-protected HCMs from hypoxia-induced cell injury by regulating miR-191-5p/TRAF3 signaling, which might provide some convincing evidences for further understanding the influences of “lncRNA-miRNA-mRNA” network in the development of MI.