Drug Design, Development and Therapy (2021-02-01)

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

  • Wang H,
  • Lin X,
  • Li J,
  • Zeng G,
  • Xu T

Journal volume & issue
Vol. Volume 15
pp. 481 – 492

Abstract

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Haining Wang,1 Xiule Lin,1 Jilin Li,2 Guoning Zeng,1 Tan Xu1 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Shantou University Medical College, Cardiac Care Unit (CCU), Shantou, Guangdong Province, 515041, People’s Republic of China; 2Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, 515000, People’s Republic of ChinaCorrespondence: Haining WangDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Shantou University Medical College, CCU, Shantou City, Guangdong Province, 515041, People’s Republic of ChinaTel +86-(0754)88258290Email [email protected] LiDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, 515000, People’s Republic of ChinaEmail [email protected]: 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: lncRNA SOX2-OT, miR-942-5p, DP5, cardiomyocyte, apoptosis

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