Anti-apoptotic Effect of MiR-223-3p Suppressing PIK3C2A in Cardiomyocytes from Myocardial Infarction Rat Through Regulating PI3K/Akt Signaling Pathway.

Liu Xiaoyu, Zhang Wei, Zhao Ming, Jia Guowei

Cardiovascular toxicology 2021 Aug

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We aimed to explore the regulatory mechanism of the axis of miR-223-3p-PIK3C2A-PI3K/Akt on cardiomyocyte apoptosis in rats with myocardial infarction. Thirty 8-week-old healthy male SD rats were used for establishing the sham group and the model group, with HE staining, TUNEL staining, and TTC staining performed. After the identification of the targeting relationship between PIK3C2A and miR-223-3p, experimental rats were randomly divided into seven groups by plasmid transfection, including the Blank group, negative control (NC) group, miR-223-3p mimic group, miR-223-3p inhibitor group, siRNA-PIK3C2A group, oe-PIK3C2A group, and miR-223-3p inhibitor + oe-PIK3C2A group. Four weeks after transfection, the expression levels of miR-223-3p and PIK3C2A in tissues as well as PI3K, Akt, Bax, and bcl-2 mRNA in cells were detected by qRT-PCR and western blot, in combination with the detection of apoptosis rate by flow cytometry. Compared with the sham group, the model group showed typical myocardial injury and abnormal staining, higher apoptotic index, and larger myocardial infarction area (all P < 0.05). PIK3C2A was the target gene of miR-223-3p. The expression level of miR-223-3p in model group was significantly lower than that in sham group, while the mRNA and protein expression levels of PIK3C2A increased significantly (all P < 0.05). In cell tests, the expression level of miR-223-3p increased significantly in miR-223-3p mimic group (P < 0.05), which, however, showed no significant change in siRNA-PIK3C2A group (P > 0.05). MiR-223-3p inhibitor group and siRNA-PIK3C2A group had obviously increased PI3K, Akt, mTOR and Bcl-2 mRNA, and protein expression, while decreased mRNA and protein expression of PIK3C2A and Bax (all P < 0.05); miR-223-3p mimic groups had the opposite trends (all P < 0.05). siRNA-PIK3C2A + miR-223-3p mimic showed no obvious change relative to the control groups (all P > 0.05). Low expression of miR-223-3p may downregulate PIK3C2A expression, resulting in the inhibition of myocardial cell apoptosis in rats with myocardial infarction via the activation of PI3K/Akt signaling pathway.

Citation

Liu Xiaoyu, Zhang Wei, Zhao Ming, Jia Guowei. Anti-apoptotic Effect of MiR-223-3p Suppressing PIK3C2A in Cardiomyocytes from Myocardial Infarction Rat Through Regulating PI3K/Akt Signaling Pathway. Cardiovascular toxicology. 2021 Aug;21(8):669-682