Journal article
Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner
A Zhuang, AC Calkin, S Lau, H Kiriazis, DG Donner, Y Liu, ST Bond, SC Moody, EAM Gould, TD Colgan, SR Carmona, M Inouye, TQ de Aguiar Vallim, EJ Tarling, GA Quaife-Ryan, JE Hudson, ER Porrello, P Gregorevic, XM Gao, XJ Du Show all
Iscience | Published : 2021
Open access
Abstract
Long non-coding RNAs (lncRNAs) have been demonstrated to influence numerous biological processes, being strongly implicated in the maintenance and physiological function of various tissues including the heart. The lncRNA OIP5-AS1 (1700020I14Rik/Cyrano) has been studied in several settings; however its role in cardiac pathologies remains mostly uncharacterized. Using a series of in vitro and ex vivo methods, we demonstrate that OIP5-AS1 is regulated during cardiac development in rodent and human models and in disease settings in mice. Using CRISPR, we engineered a global OIP5-AS1 knockout (KO) mouse and demonstrated that female KO mice develop exacerbated heart failure following cardiac press..
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Awarded by State Government of Victoria
Funding Acknowledgements
We acknowledge funding support from the Victorian State Government OIS program to Baker Heart & Diabetes Institute (BHDI). These studies were supported in part by funding from the National Health & Medical Research Council (NHMRC) of Australia to B.G.D. and J.R.M. (APP1127336). B.G.D. and A.C.C. received funding from the National Heart Foundation of Australia, via the Future Leader Fellowship Scheme (101789 and 100067, respectively). J.R.M. and P.G. are Research Fellows of the NHMRC (APP1078985 and APP1117835, respectively). We acknowledge the use of facilities and technical assistance from the Monash Histology Platform, Department of Anatomy and Developmental Biology, Monash University, and use of the gene set enrichment analysis (GSEA) software, and Molecular Signature Database (MSigDB) (Subramanian et al., 2005). We thank all members of the Cardiac Hypertrophy, MMA, and LMCD laboratories at BHDI for their ongoing contributions.