title: MicroRNA-297 promotes cardiomyocyte hypertrophy via targeting sigma-1 receptor.
abstract: OBJECTIVE
  Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy.
  
  
  METHODS
  Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R. Transverse aortic constriction (TAC) model and neonatal rat cardiomyocytes (NCMs) stimulated with angiotensin II (AngII) were used to explore the relationship between miR-297 and Sig-1R. Additionally, the function of miR-297 in cardiomyocyte hypertrophy and ER stress/unfolded protein response (UPR) signaling pathway was investigated by transfecting miR-297 mimics/inhibitor.
  
  
  RESULTS
  miR-297 levels were increased in both TAC-induced hypertrophic heart tissue and AngII-induced cardiomyocyte hypertrophy. Up-regulation of miR-297 by specific mimics exacerbated AngII-induced cardiomyocyte hypertrophy, whereas inhibition of miR-297 suppressed the process. During cardiomyocyte hypertrophy, Sig-1R expression, which was negatively regulated by miR-297 by directly targeting its 3'untranslated region (UTR), was decreased. Furthermore, attenuation of miR-297 inhibited the activation of X-box binding protein 1 (Xbp1) and activating transcriptional factor 4 (ATF4) signaling pathways in NCMs.
  
  
  CONCLUSIONS
  Our data demonstrate that miR-297 promotes cardiomyocyte hypertrophy by inhibiting the expression of Sig-1R and activation of ER stress signaling, which provides a novel interpretation for cardiac hypertrophy.
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Bao
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liuxq@scu.edu.cn.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019295:Computational Biology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000096:biosynthesis*; D015398:Signal Transduction; D056811:Unfolded Protein Response; D000097605:Sigma-1 Receptor
chemical_list: D035683:MicroRNAs; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: Cardiac hypertrophy; Endoplasmic reticulum stress; Sigma-1 receptor; miR-297