HOTAIR functions as a competing endogenous RNA to regulate PTEN expression by inhibiting miR-19 in cardiac hypertrophy

• Published in: Molecular and cellular biochemistry Vol. 432; no. 1-2; pp. 179 - 187
• Main Authors: Lai, Yanjun, He, Shuai, Ma, Liming, Lin, Hong, Ren, Biyun, Ma, Jing, Zhu, Xinyu, Zhuang, Shifang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biological activity; Biomedical and Life Sciences; Cardiology; Cardiomegaly - chemically induced; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomyocytes; Cell surface; Cells; Eutrophication; Gene expression; Gene Expression Regulation, Enzymologic; Health aspects; Heart; Heart diseases; Heart failure; Heart hypertrophy; Hypertrophy; In vitro methods and tests; Life Sciences; Major histocompatibility complex; Male; Medical Biochemistry; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular modelling; Oncology; Physiological aspects; Polymerase chain reaction; PTEN Phosphohydrolase - biosynthesis; PTEN Phosphohydrolase - genetics; PTEN protein; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Stimulation; HOTAIR; Cardiac hypertrophy; PTEN; MiR-19; Competing endogenous RNA
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-017-3008-y

Sustained cardiac hypertrophy (CH) is related to a variety of physiological as well as pathological stimuli and eventually increases the risk of heart failure. HOTAIR has been identified as a competing endogenous RNA in multiple human biological processes. Whether lncRNA-HOTAIR is involved in the progress of CH and how it works still remain unknown. Herein, we found that HOTAIR was down-regulated, while miR-19 was up-regulated in both heart tissues from TAC-operated mice in vivo and cultural cardiomyocytes treated with Ang-II in vitro by real-time PCR. Meanwhile, HOTAIR expression was negatively correlated with miR-19 in TAC-operated mice. HOTAIR overexpression reduced cell surface area and the expression of hypertrophic markers ANP, BNP, and β-MHC in response to Ang-II stimulation as well as knockdown of miR-19. The further molecular mechanisms of HOTAIR action in CH demonstrated that HOTAIR may act as a competing endogenous RNA (ceRNA) for miR-19, thereby modulating the dis-inhibition of its endogenous target PTEN and playing an important role in inhibiting CH progress. These findings reveal a novel function of LncRNAs, which conduce to an extensive understanding of CH and provide novel research directions and therapeutic options for treating this disease.