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Inhibition of lncRNA DANCR Prevents Heart Failure by Ameliorating Cardiac Hypertrophy and Fibrosis Via Regulation of the miR-758-3p/PRG4/Smad Axis

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Abstract

The current work was developed to explore the functions and possible mechanism of PRG4 in cardiac hypertrophy and heart failure. Ang II-stimulated H9c2 cells and AC16 cells were used as in vitro cell models. The binding relation between genes in cells was explored using luciferase reporter assays and RNA immunoprecipitation assay. The cardiac functions of rats received transverse-ascending aortic constriction (TAC) surgery and adeno-associated virus (AAV) injection were examined with echocardiography. The myocardial histological changes were observed using H&E, wheat germ agglutinin, and sirius red staining. It was discovered that PRG4 silencing attenuated cell hypertrophy and fibrosis and inactivated the Smad pathway under Ang II treatment. PRG4 was targeted by miR-758-3p, and miR-758-3p interacted with long noncoding RNA DANCR. DANCR silencing inhibited cardiac dysfunction, fibrosis, and TGFβ1/Smad pathway. In addition, DANCR was highly expressed in myocardial extracellular vesicles. Overall, DANCR depletion prevents heart failure by inhibiting cardiac hypertrophy and fibrosis via the miR-758-3p/PRG4/Smad pathway.

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All data generated or analyzed during this study are included either in this article or in the supplementary information.

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Authors and Affiliations

  1. Department of Cardiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, China

    Qianwen Huang

  2. Teaching and Research Section of Physiology, Basic Medicine Department, Quanzhou Medical College, No.2 Anji Road, Luojiang District, Quanzhou, 362000, Fujian, China

    Qian Huang

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Contributions

Qianwen Huang was the main designer of this study. Qianwen Huang and Qian Huang performed the experiments and analyzed the data. Qianwen Huang and Qian Huang drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qian Huang.

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Ethical Approval

The protocol of in vivo assays was in approval of the ethics committee of Quanzhou Medical College and was performed following The Guide for the Care and Use of Laboratory Animals (National Institutes of Health, USA).

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The authors declare no competing interests.

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Associate Editor Guoping Li oversaw the review of this article.

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Huang, Q., Huang, Q. Inhibition of lncRNA DANCR Prevents Heart Failure by Ameliorating Cardiac Hypertrophy and Fibrosis Via Regulation of the miR-758-3p/PRG4/Smad Axis. J. of Cardiovasc. Trans. Res. 16, 1357–1372 (2023). https://doi.org/10.1007/s12265-023-10428-z

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  • DOI: https://doi.org/10.1007/s12265-023-10428-z

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