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

Mol Cell Biochem. 2017 Aug;432(1-2):179-187. doi: 10.1007/s11010-017-3008-y. Epub 2017 Mar 18.

Abstract

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.

Keywords: Cardiac hypertrophy; Competing endogenous RNA; HOTAIR; MiR-19; PTEN.

MeSH terms

  • Animals
  • Cardiomegaly / chemically induced
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Gene Expression Regulation, Enzymologic*
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PTEN Phosphohydrolase / biosynthesis*
  • PTEN Phosphohydrolase / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • HOTAIR long non-coding RNA, mouse
  • MIRN19 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • Pten protein, mouse