Sirt1 Antisense Long Noncoding RNA Promotes Cardiomyocyte Proliferation by Enhancing the Stability of Sirt1

J Am Heart Assoc. 2018 Nov 6;7(21):e009700. doi: 10.1161/JAHA.118.009700.

Abstract

Background Antisense long noncoding RNAs (lnc RNA s) are single-stranded RNA s that overlapped gene-coding regions on the opposite DNA strand and play as critical regulators in cardiovascular diseases. The high conservation and stability may be good advantages for antisense lnc RNA s. However, the roles of antisense lnc RNA s in cardiomyocyte proliferation and cardiac regeneration are still unknown. Methods and Results In this study, we found that Silent information regulator factor 2 related enzyme 1 (Sirt1) antisense lnc RNA expression was significantly increased during heart development. By gain and loss function of Sirt1 antisense lnc RNA using adenovirus and locked nucleic acid, respectively, we demonstrated that Sirt1 antisense lnc RNA promoted cardiomyocyte proliferation in vitro and in vivo, and the suppression of Sirt1 antisense lnc RNA inhibited cardiomyocyte proliferation. Moreover, overexpression of Sirt1 antisense lnc RNA enhanced cardiomyocyte proliferation, attenuated cardiomyocyte apoptosis, improved cardiac function, and decreased mortality rate after myocardial infarction. Furthermore, Sirt1 antisense lnc RNA can bind the Sirt1 3'-untranslated region, enhancing the stability of Sirt1 and increasing Sirt1 abundance at both the mRNA and protein levels. Finally, we found that Sirt1 was involved in Sirt1 antisense lnc RNA -induced cardiomyocyte proliferation. Conclusions The present study identified Sirt1 antisense lnc RNA as a novel regulator of cardiomyocyte proliferation and cardiac regeneration by interacting and stabilizing Sirt1 mRNA , which may serve as an effective gene target for preventing myocardial infarction.

Keywords: Sirt1; Sirt1 antisense lncRNA; cardiac regeneration; cardiomyocyte proliferation; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / cytology*
  • RNA, Antisense / physiology*
  • RNA, Long Noncoding / physiology*
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / physiology*

Substances

  • RNA, Antisense
  • RNA, Long Noncoding
  • Sirt1 protein, mouse
  • Sirtuin 1