The long non-coding RNA TUG1-miR-9a-5p axis contributes to ischemic injuries by promoting cardiomyocyte apoptosis via targeting KLF5

• Published in: Cell death & disease Vol. 10; no. 12; p. 908
• Main Authors: Yang, Di, Yu, Jie, Liu, Hui-Bin, Yan, Xiu-Qing, Hu, Juan, Yu, Yang, Guo, Jing, Yuan, Ye, Du, Zhi-Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.12.2019; Springer Nature B.V
• Subjects: 13/109; 13/2; 3' Untranslated Regions - genetics; 59; 631/337/384/2568; 631/443/592/75; 64; 64/60; 82/1; 82/80; Animals; Antibodies; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Base Sequence; Biochemistry; Biomedical and Life Sciences; Cardiomyocytes; Cell Biology; Cell Culture; Cell Survival - drug effects; Chromosome 5; Down-Regulation - drug effects; Heart; Heart attacks; HEK293 Cells; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Immunology; Ischemia; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Life Sciences; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Mitochondria; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - pathology; Myocardial Ischemia - genetics; Myocardial Ischemia - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Non-coding RNA; Rats; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-mediated interference; Taurine
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-2138-4

Non-coding RNAs participate in many cardiac pathophysiological processes, including myocardial infarction (MI). Here we showed the interplay between long non-coding RNA taurine-upregulated gene 1 (lncR-TUG1), miR-9a-5p (miR-9) and Krüppel-like factor 5 (KLF5). LncR-TUG1 was upregulated in ischemic heart and in cultured cardiomyocytes exposed to H 2 O 2 . Knockdown of lncR-TUG1 markedly ameliorated impaired cardiac function of MI mice. Further study showed that lncR-TUG1 acted as a competitive endogenous RNA of miR-9, and silencing of lncR-TUG1 inhibited cardiomyocyte apoptosis by upregulating miR-9 expression. Furthermore, the miR-9 overexpression obviously prevented ischemia injury and significantly inhibited H 2 O 2 -induced cardiomyocyte apoptosis via inhibition of mitochondrial apoptotic pathway. KLF5, as a target gene of miR-9 by dual-luciferase reporter assay, was involved in the process of miR-9 in regulating cardiomyocyte apoptosis. Our data identified the KLF5 was downregulated by miR-9 overexpression and knockdown of KLF5 inhibited cardiomyocyte apoptosis induced by H 2 O 2 . MiR-9 exerts anti-cardiomyocyte apoptotic affects by targeting KLF5. Collectively, our data identify a novel function of lncR-TUG1/miR-9/KLF5 axis in regulating cardiomyocyte apoptosis that affects myocardial infarction progression.