Long Noncoding RNA SOX2-OT Aggravates Doxorubicin-Induced Apoptosis of Cardiomyocyte by Targeting miR-942-5p/DP5

Drug Des Devel Ther. 2021 Feb 11:15:481-492. doi: 10.2147/DDDT.S267474. eCollection 2021.

Abstract

Background: Long non-coding RNAs (LncRNAs) play important roles in doxorubicin (DOX)-induced apoptosis of cardiomyocytes. However, the function of lncRNA SOX2-OT is unclear. This study was carried out to investigate the function of SOX2-OT in doxorubicin-induced cardiomyocyte apoptosis.

Methods: qRT-PCR and immunoblotting were used to detect the expression levels of SOX2-OT, miR-942-5p and death protein-5 (DP5) in DOX-treated primary cardiomyocytes and rat models. The relationship among miR-942-5p, SOX2-OT, and DP5 was explored by luciferase reporter assay. The effects of SOX2-OT, miR-942-5p and DP5 on doxorubicin-induced cardiomyocyte apoptosis were evaluated by Annexin V-FITC/PI method and caspase-3 activity assay. The effect of SOX2-OT on cardiomyocyte apoptosis was analyzed by TUNEL staining and echocardiography.

Results: SOX2-OT and DP5 were highly expressed, while miR-942-5p was down-regulated in DOX-treated primary cardiomyocytes and rat model. SOX2-OT can upregulate DP5 as a sponge of miR-942-5p, which was a direct target of miR-942-5p. In addition, miR-942-5p reversed the protective effect of knockdown of SOX2-OT on cardiomyocytes by inhibiting the expression of DP5 in vitro and in vivo.

Conclusion: Knockdown of SOX2-OT down-regulated DP5 via sponging miR-942-5p and inhibiting DOX-induced apoptosis of primary cardiomyocytes.

Keywords: DP5; apoptosis; cardiomyocyte; lncRNA SOX2-OT; miR-942-5p.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Structure
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Apoptosis Regulatory Proteins
  • Hrk protein, rat
  • MicroRNAs
  • Neuropeptides
  • RNA, Long Noncoding
  • Doxorubicin

Grants and funding

This study received the financial support from Natural science foundation of Guangdong Province (2015A030313441). Funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.