title: The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.
abstract: BACKGROUND
  Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years.
  
  
  OBJECTIVE
  We identified miR-489 and lncRNAs (cardiac hypertrophy related factor, CHRF) from hypertrophic cardiomyocytes. Here, we tested the hypothesis that miR-489 and CHRF can participate in the regulation of cardiac hypertrophy in vivo and in vitro.
  
  
  RESULTS
  A microarray was performed to analyze miRNAs in response to angiotensin II treatment, and we found miR-489 was substantially reduced. Enforced expression of miR-489 in cardiomyocytes and transgenic overexpression of miR-489 both exhibited reduced hypertrophic response on angiotensin II treatment. We identified myeloid differentiation primary response gene 88 (Myd88) as a miR-489 target to mediate the function of miR-489 in cardiac hypertrophy. Knockdown of Myd88 in cardiomyocytes and Myd88-knockout mice both showed attenuated hypertrophic responses. Furthermore, we explored the molecular mechanism by which miR-489 expression is regulated and found that an lncRNA that we named CHRF acts as an endogenous sponge of miR-489, which downregulates miR-489 expression levels. CHRF is able to directly bind to miR-489 and regulate Myd88 expression and hypertrophy.
  
  
  CONCLUSIONS
  Our present study reveals a novel cardiac hypertrophy regulating model that is composed of CHRF, miR-489, and Myd88. The modulation of their levels may provide a new approach for tackling cardiac hypertrophy.
authors.affiliation: From the Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Lu-Yu
authors.initials: LY
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Yuan
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Liu
authors.forename: Teng
authors.initials: T
authors.lastname: Sun
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Li
mesh_terms: D000804:Angiotensin II; D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: C000588951:CHRF long noncoding RNA, human; C570982:MIRN489 microRNA, mouse; D035683:MicroRNAs; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009841:Oligonucleotides; D062085:RNA, Long Noncoding; D000804:Angiotensin II
keywords: RNA, long noncoding; cardiomegaly