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  • Title: miR-181b-5p suppresses starvation-induced cardiomyocyte autophagy by targeting Hspa5.
    Author: Chang L, Chai X, Chen P, Cao J, Xie H, Zhu J.
    Journal: Int J Mol Med; 2019 Jan; 43(1):143-154. PubMed ID: 30431062.
    Abstract:
    This study aimed to investigate the role of microRNA‑181b‑5p (miR‑181b‑5p) in starvation‑induced cardiomyocyte autophagy by targeting heat shock protein family A member 5 (Hspa5). For this purpose, H9c2 cardiomyocytes and neonatal rat ventricular myocytes (NRVMs) were glucose‑starved in Earle's Balanced Salt Solution (EBSS) for different periods of time (0, 2, 4, 6 and 8 h). RT‑qPCR analysis was performed to examine the expression of miR‑181b‑5p in the different groups. Immunofluorescence was performed to detect the expression of LC3. In addition, the H9c2 cardiomyocytes and NRVMs were transfected with miR‑181b‑5p mimic, miR‑181b‑5p inhibitor, siHspa5 or their respective controls. An MTT assay was performed to measure cell proliferation in the different groups. Western blot analysis was performed to determine the expression of Beclin‑1, Hspa5, phosphorylated phosphoinositide 3‑kinase PI3K (p‑PI3K), phosphorylated Akt (p‑Akt), phosphorylated mammalian target of rapamycin (p‑mTOR), Bcl‑2, Bax and cleaved caspase‑3. Flow cytometry was performed to assess cell apoptosis. A luciferase reporter assay was performed to determine whether Hspa5 is a direct target of miR‑181b‑5p. The results revealed that the downregulation of miR‑181b‑5p promoted cell autophagy in the cardiomyocytes. Moreover, miR‑181b‑5p negatively regulated Beclin‑1 and Hspa5. Beclin‑1 is a well‑known autophagy‑ and apoptosis‑related protein. In addition, cell apoptosis was attenuated by the decreased expression of miR‑181b‑5p in the cardiomyocytes. Bcl‑2 prevented apoptosis and autophagy by binding to Bax and Bcl‑2, respectively. The upregulation of miR‑181b‑5p inhibited autophagy and promoted apoptosis via Hspa5. miR‑181b‑5p inhibition promoted p‑mTOR, p‑Akt and p‑PI3K expression via Hspa5. The results of luciferase reporter assay also confirmed that Hspa5 is a direct target of miR‑181b‑5p. On the whole, the findings of this study suggest that miR‑181b‑5p contributes to starvation‑induced autophagy and apoptosis in cardiomyocytes by directly targeting Hspa5 via the PI3K/Akt/mTOR signaling pathway.
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