科研之友
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AIM：To investigate the effect of circular RNA MYO9A-006（circMYO9A_006）on hypertrophic phenotype of cardiomyocytes and the underlying mechanism. METHODS：The effect of adenovirus-mediated overexpres? sion of circMYO9A_006 on the expression of hypertrophy-related proteins，including β-myosin heavy chain（β-MHC），skeletal muscle actin alpha 1（ACTA1）and atrial natriuretic peptide（ANP），was evaluated in neonatal mouse ventricular cardiomyocytes（NMVCs）. Moreover，a neonatal rat ventricular cardiomyocyte（NRVC）model of phenylephrine（PE）-in? duced hypertrophy was established. The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method. Dual-luciferase reporter assay was employed to measure the activity of potential in? ternal ribosome entry sites（IRES）in circMYO9A_006. The translation and intracellular location of the circMYO9A_006-translated protein，MYO9A-208aa，were verified using Western blot. To investigate the role of MYO9A-208aa in the ef? fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype，we prepared and used the following adenoviruses：the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa，the recombinant circMYO9A_006-ATGmut adenovirus that does not express MYO9A-208aa，the recombinant circMYO9A_006 adenovirus，and the adenovirus vector control. These were then employed to infect NRVCs. RESULTS：Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs. The increased expression of circMYO9A_006 notably reduced the expres? sion of hypertrophy-related proteins in NMVCs（P<0. 01）. Concurrently，overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs（P<0. 05）. Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006. Western blot results indicated that circ? MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs，primari? ly found in the cytoplasm. Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex? pression of hypertrophy-associated proteins（P<0. 01），and counteracted the enlarged size of PE-induced NRVCs（P< 0. 05）. However，increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe? notype of NRVCs. CONCLUSION：circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe? sizing the MYO9A-208aa protein. ? 2024 Editorial Board of Chinese Journal of Pathophysiology, Jinan University.
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