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J Cell Mol Med. 2019 Aug 29. doi: 10.1111/jcmm.14641. [Epub ahead of print]

Long non-coding RNA cardiac hypertrophy-associated regulator governs cardiac hypertrophy via regulating miR-20b and the downstream PTEN/AKT pathway.

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Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Center of Chronic Diseases and Drug Research of Mudanjiang Medical, University of Alliance of Sino-Russian Medical Universities, Mudanjiang Medical University, Mudanjiang, China.
Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, China.


Pathological cardiac hypertrophy (CH) is a key factor leading to heart failure and ultimately sudden death. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation relevant to a wide spectrum of human disease including cardiac disorders. Here, we characterize the role of a specific lncRNA named cardiac hypertrophy-associated regulator (CHAR) in CH and delineate the underlying signalling pathway. CHAR was found markedly down-regulated in both in vivo mouse model of cardiac hypertrophy induced by pressure overload and in vitro cellular model of cardiomyocyte hypertrophy induced by angiotensin II (AngII) insult. CHAR down-regulation alone was sufficient to induce hypertrophic phenotypes in healthy mice and neonatal rat ventricular cells (NRVCs). Overexpression of CHAR reduced the hypertrophic responses. CHAR was found to act as a competitive endogenous RNA (ceRNA) to down-regulate miR-20b that we established as a pro-hypertrophic miRNA. We experimentally established phosphatase and tensin homolog (PTEN), an anti-hypertrophic signalling molecule, as a target gene for miR-20b. We found that miR-20b induced CH by directly repressing PTEN expression and indirectly increasing AKT activity. Moreover, CHAR overexpression mitigated the repression of PTEN and activation of AKT by miR-20b, and as such, it abrogated the deleterious effects of miR-20b on CH. Collectively, this study characterized a new lncRNA CHAR and unravelled a new pro-hypertrophic signalling pathway: lncRNA-CHAR/miR-20b/PTEN/AKT. The findings therefore should improve our understanding of the cellular functionality and pathophysiological role of lncRNAs in the heart.


cardiac hypertrophy; cardiac hypertrophy-associated regulator; long non-coding RNA; miR-20b; phosphatase and tensin homolog

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