• Ying Gu, Boyao Zhang, Yongchao Yu, Fan Yang, Yuchen Xiao, Weisheng Chen, Liping Ma, Weizhong Wang, and Guokun Wang.
• Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
• J. Investig. Med. 2021 Mar 1; 69 (3): 749-755.

AbstractCardiomyocyte hypertrophy is a response to stress or hormone stimulation and is characterized by an increase of cardiomyocyte size. Abnormal long non-coding RNA (lncRNA) expression profile has been identified in various cardiovascular diseases. Though some lncRNAs had been reported to participate in regulation of cardiac hypertrophy, the universal lncRNA profile of cardiomyocyte hypertrophy had not been established. In the present study, we aimed to identify the differentially expressed lncRNA-mRNA network in angiotensin II-stimulated cardiomyocytes, and screen the potential lncRNAs involved in regulation of cardiomyocyte hypertrophy. The hypertrophic cardiomyocytes were induced by angiotensin II (0.1 μmol/L) for 48 hours. High-throughput microarray analysis combined with quantitative real-time PCR assay were then performed to screen the differentially expressed lncRNAs and mRNAs. A total of 1577 lncRNAs and 496 mRNAs transcripts were identified differentially expressed in hypertrophic cardiomyocytes. Among them, 59 transcribed ultraconserved non-coding RNAs (T-UCRs) were found by evolutionary conservation analysis. Subsequently, the lncRNA-mRNA coexpression network was constructed based on Pearson's correlation analysis results, including 4 T-UCRs and 215 mRNAs. The results revealed that uc.242 was positively interacted with prohypertrophic genes (Hgf and Tnc). Functional study showed that inhibition of uc.242 dramatically decreased hypertrophic marker expression levels and cardiomyocyte surface area under the condition of angiotensin II stimulation. The expression of Hgf and Tnc was also decreased in cardiomyocytes after silencing of uc.242. Summarily, the present study provided crucial clues to explore therapeutic targets for pathological cardiac hypertrophy.© American Federation for Medical Research 2021. No commercial re-use. See rights and permissions. Published by BMJ.

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