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miR-145-5p targets paxillin to attenuate angiotensin II-induced pathological cardiac hypertrophy via downregulation of Rac 1, pJNK, p-c-Jun, NFATc3, ANP and by Sirt-1 upregulation

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Abstract

Pathological cardiac hypertrophy is associated with many diseases including hypertension. Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-145-5p in the cardiac setting is still unclear. In this study, H9C2 cells were overexpressed with microRNA-145-5p, and then treated with Ang-II for 24 h, to study the effect of miR-145-5p on Ang-II-induced myocardial hypertrophy in vitro. Results showed that Ang-II treatment down-regulated miR-145-5p expression were revered after miR-145-5p overexpression. Based on results of bioinformatics algorithms, paxillin was predicted as a candidate target gene of miR-145-5p, luciferase activity assay revealed that the luciferase activity of cells was substantial downregulated the following co-transfection with wild paxillin 3′UTR and miR-145-5p compared to that in scramble control, while the inhibitory effect of miR-145-5p was abolished after transfection of mutant paxillin 3′UTR. Additionally, overexpression of miR-145-5p markedly inhibited activation of Rac-1/ JNK /c-jun/ NFATc3 and ANP expression and induced SIRT1 expression in Ang-II treated H9c2 cells. Jointly, our study suggested that miR-145-5p inhibited cardiac hypertrophy by targeting paxillin and through modulating Rac-1/ JNK /c-jun/ NFATc3/ ANP / Sirt1 signaling, therefore proving novel downstream molecular pathway of miR-145-5p in cardiac hypertrophy

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Funding

“This research was funded by Taiwan Department of Health Clinical Trial and Research Centre of Excellence; grant number MOHW107-TDU-B-212-123004 and DMR-109-059 (China Medical University Hospital)”.

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Author notes

  1. Yu-Lan Yeh and Chih-Yang Huang share equal contribution.

Authors and Affiliations

  1. Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan

    Kuan-Ho Lin

  2. College of Medicine, China Medical University, Taichung, Taiwan

    Kuan-Ho Lin

  3. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan

    V. Bharath Kumar & Chih-Yang Huang

  4. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tamilselvi Shanmugam, Marthandam Asokan Shibu & Chih-Yang Huang

  5. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan

    Ray-Jade Chen

  6. Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan

    Chia-Hua Kuo

  7. Chinese Medicine, Hualien Tzu Chi Hospital, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  8. Department of Biotechnology, Bharathiar University, Coimbatore, 641046, India

    V. Vijaya Padma

  9. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan

    Yu-Lan Yeh

  10. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Taipei, 11260, Taiwan

    Yu-Lan Yeh

  11. Center of General Education, Tzu Chi University of Science and Technology, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan

    Chih-Yang Huang

  12. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan

    Chih-Yang Huang

  13. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan

    Chih-Yang Huang

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  1. Kuan-Ho Lin
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Lin, KH., Kumar, V.B., Shanmugam, T. et al. miR-145-5p targets paxillin to attenuate angiotensin II-induced pathological cardiac hypertrophy via downregulation of Rac 1, pJNK, p-c-Jun, NFATc3, ANP and by Sirt-1 upregulation. Mol Cell Biochem 476, 3253–3260 (2021). https://doi.org/10.1007/s11010-021-04100-w

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