The long noncoding RNA THRIL knockdown protects hypoxia-induced injuries of H9C2 cells through regulating miR-99a
Authors: Nianxin Jiang
Yong Wei
Jingwen Xia
Xuan Zhang
Yansong Li
Journal: Cardiology Journal (2019)
Discipline: CLINICAL MEDICINE
Keywords: Brg1; THRIL; hypoxia; miR-99a; myocardial infarction.
Affiliations: Department of Cardiovasology, Shanghai Songjiang District Center Hospital, Shanghai, China., Department of Cardiology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China., Department of Cardiovasology, Shanghai Songjiang District Center Hospital, Shanghai, China. .

Abstract:  Background: Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in heart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells. Methods: THRIL, miR-99a and Brahma-related gene 1 (Brg1) expressions in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated. Cell viability, migration and invasion, and apoptotic cells were respectively measured by trypan blue exclusion assay, transwell migration assay and flow cytometry assay. Dual luciferase reporter assay was conducted to verify the interaction between miR-99a and THRIL. Furthermore, levels of apoptosis-, PI3K/AKT and mTOR pathways-related factors were measured by western blotting. Results: Hypoxia induced an increase of THRIL but a reduction of miR-99a and Brg1. THRIL inhibition significantly attenuated hypoxia-induced cell injuries, as increased cell viability, migration and invasion, and decreased cell apoptosis. THRIL negatively regulated miR-99a expression through sponging with miR-99a binding site, and miR-99a inhibition abolished the protective effects of THRIL knockdown against hypoxia-induced injury in H9C2 cells. Furthermore, miR-99a positively regulated the expression of Brg1. Brg1 inhibition promoted hypoxia-induced cell injuries, while Brg1 overexpression alleviated hypoxia-induced cell injuries. Moreover, Brg1 overexpression activated PI3K/AKT and mTOR pathways. Conclusions: This study demonstrated that THRIL inhibition represented a protective effect against hypoxia-induced injuries in H9C2 cells by up-regulating miR-99a expression. 

Retracted: No

PubPeer comments:
 The affiliation of the corresponding author is represented as a single affiliation: u201c4Department of Orthopaedic Surgery, Louisiana State University Medical Center, New Orleans, LA, Medical Affairs, Bioventus LLC, 4721 Emperor Blvd., Suite 100, Durham, NC 27703u201d However, close examination reveals two affiliations, one in Louisiana, the other in North Carolina: 4. Department of Orthopaedic Surgery, Louisiana State University Medical Center, New Orleans, LA 5. Medical Affairs, Bioventus LLC, 4721 Emperor Blvd., Suite 100, Durham, NC 27703 The correct representation should have thus been: R. Grant Steen 4,5* In addition, this article does not have a conflict of interest statement, which should have included, for the corresponding author, this affiliation: 2. President, MediCC!, Medical Communications Consultants LLC http: medicalcommunicationsconsultants.com , 
 P.S. The listed address for Medical Communications Consultants LLC, which does not appear on the company website, but does appear on Google Maps, is: 103 Van Doran Pl, Chapel Hill, NC 27517 ,