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DSCAM-AS1 mediates pro-hypertrophy role of GRK2 in cardiac hypertrophy aggravation via absorbing miR-188-5p

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Abstract

Sustained cardiac hypertrophy, as previously clarified, serves as a critical initiator of heart failure and therefore is acknowledged as an important factor for heart failure treatment. The broadly demonstrated function and participation of long non-coding RNAs (lncRNAs) in tumors are well accepted. However, the underlying mechanism implicating lncRNAs in cardiac hypertrophy is mostly unexplored and deserves to be specifically studied. The devised work was aimed to disclose the function of lncRNA DS cell adhesion molecule antisense RNA 1 (DSCAM-AS1) in angiotensin II (AngII)-induced cardiac hypertrophy. In this study, we discovered the upregulation of DSCAM-AS1 in cardiomyocytes treated with AngII by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot and qRT-PCR suggested that DSCAM-AS1 silencing attenuated the highly expressed hypertrophic biomarkers including β-myosin heavy chain (β-MHC), brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) at mRNA and protein levels. The expanded cell surface in the presence of AngII treatment area was also shrunk by DSCAM-AS1 silencing. Mechanical analysis manifested that DSCAM-AS1 sponged microRNA-188-5p to boost the pro-hypertrophy gene G protein-coupled receptor kinase 2 (GRK2) expression. Rescue experiments unveiled miR-188-5p and GRK2 managed to reverse the anti-hypertrophy impact of DSCAM-AS1 silencing. In summary, DSCAM-AS1 was identified as a positive modulator in cardiac hypertrophy through miR-188-5p decoying and GRK2 augmentation, giving rise to an enriched theoretical basis for finding a promising target in cardiac hypertrophy regulation.

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Acknowledgments

We appreciate the aids from all participators in this work.

Funding

This study was supported by the Project of Fujian Provincial Department of Education (JA15717) and Quanzhou Science and Technology Project (2015Z98).

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Authors and Affiliations

  1. Department of Basic Medical, Quanzhou Medical College, No. 2 Anji Road, Luojiang District, Quanzhou City, 362011, Fujian Province, China

    Huiqin Chen

  2. Cardiovascular Department, The Second Affiliated Hospital of Fujian Medical University, No. 34 Zhongshan North Road, Quanzhou City, 362000, China

    Kefeng Cai

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  1. Huiqin Chen
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  2. Kefeng Cai
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Correspondence to Kefeng Cai.

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Editor: Tetsuji Okamoto

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Chen, H., Cai, K. DSCAM-AS1 mediates pro-hypertrophy role of GRK2 in cardiac hypertrophy aggravation via absorbing miR-188-5p. In Vitro Cell.Dev.Biol.-Animal 56, 286–295 (2020). https://doi.org/10.1007/s11626-020-00441-w

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  • DOI: https://doi.org/10.1007/s11626-020-00441-w

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