Abstract
Cardiomyocyte hypertrophy is a fatal factor in heart disease resulting in heart failure and even mortality. Although many studies have been focusing on the pathogenesis of cardiomyocyte hypertrophy, the exact molecular mechanisms are still unexclusive. In this study, we first found that the expression level of lncRNA Tincr was significantly decreased in the myocardial tissues of TAC mouse models of cardiomyocyte hypertrophy, and this result was further confirmed in H9C2 cells, a widely used rat myoblast cell lines. More intriguingly, we demonstrated that the aberration of Tincr is essential to the pathogenesis of cardiomyocyte hypertrophy, indicated by the re-induction of Tincr improving the heart functions of hypertrophic mice. In mechanism, we identified miR-31-5p as a direct target of Tincr using a widely used online bioinformatics tool StarBase, and this result was further experimentally validated using dual-luciferase reporter assay and real-time PCR. Also, we identified PRKCE as a direct target of miR-31-5p, and loss function of miR-31-5p significantly blocks the positive regulatory effect of Tincr on PRKCE expression in H9C2 cells. The knockdown of Tincr resulted in increased cardiomyocyte size, and, however, inhibition of miR-31-5p or overexpression of PRKCE significantly reversed the increased cardiomyocyte size. Taken together, our study showed that a novel Tincr-miR-31-5p axis targeting PRKCE was involved in cardiomyocyte hypertrophy, indicating that it may provide potential therapy in cardiomyocyte hypertrophy.
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Funding
This study was supported by the following grants: National Natural Science Foundation of China (grant no.81970204), The National Thirteenth Five-Year Project (grant no.2016YFC0903100), The Science research foundation of Shanxi Province Health and Family Planning Commission (grant no. 2017038 and 2018039), The Central Leading Local Science and Technology Development Special Fund Project (grant no.YDZX20191400004850), The Science research foundation of Shanxi Science and Technology Department (grant no. 201801D221422), 6. Ph.D Programs Foundation of the First Clinical Medical College of Shanxi Medical University (grant no. YB161704), and Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education.
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Study design: QH. Experiments and data collection: HS, HL, FZ, HX, and YZ. Data analysis and interpretation: HS. Manuscript writing: QH.
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All animal experimental procedures in this study were conducted in accordance with the guidelines of the animal ethical committee for animal experimentation in China, and the experimental design was approved by Shanxi Medical University.
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Li, H., Shi, H., Zhang, F. et al. LncRNA Tincr regulates PKCɛ expression in a miR-31-5p-dependent manner in cardiomyocyte hypertrophy. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2495–2506 (2020). https://doi.org/10.1007/s00210-020-01847-9
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DOI: https://doi.org/10.1007/s00210-020-01847-9