MicroRNA-208a Regulates H9c2 Cells Simulated Ischemia-Reperfusion Myocardial Injury via Targeting CHD9 through Notch/NF-kappa B Signal Pathways

Abstract

Ischemic reperfusion (I/R) injury is a serious problem in the treatment of ischemic heart disease. MicroRNA-208a (miR-208a) is a cardiac-specific or cardiac-enriched miRNA. This study was aimed to assess the role of miR-208a in I/R injury. H9c2 cells were used to simulate I/R injury in vitro. miR-208a expression level was measured by qPCR. H9c2 cells after simulated I/R injury were transfected with miR-208a mimic, AOS-miR-208a or negative controls. LDH release, MDA and SOD contents were measured by corresponding purchased detection kits, respectively. Cell apoptosis were measured by flow cytometry. Then binding effect of miR-208a on CHD9 3'UTR was detected by Dual-Luciferase activity assay. After miRNA or CHD9 overexpression transfections, expressions of apoptosis-related factors, CHD9, Notch 1, IκBα, and p65 in H9c2 cells after I/R injury were measured by Western blot assay. Results showed that in H9c2 cells after simulated I/R injury, miR-208a was upregulated. The elevated miR-208a expression enhanced the injury of cells and promoted cell apoptosis. miR-208a directly target 3'UTR of CHD9 and negatively regulated CHD9 expression. Overexpression of CHD9 rescued I/R injury that was enhanced by miR-208a mimic transfection. miR-208a was positively related with activation of Notch/NF-B signal pathways via CHD9. In conclusion, miR-208a was a cardiac-enriched miRNA and CHD9 is a direct target of miR-208a, which was also related with Notch/NFB signal pathway during I/R injury. miR-208a has potential to be a biomarker for early diagnosis of I/R injury and might be used as a treatment target in clinical treatment of ischemic heart disease.

miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway

“…Moreover, in a myocardial infarction model, miR-150, miR-34a, and miR-130a were found to be closely related to the occurrence of myocardial I/R injury [26]. MiR-497 was shown to be downregulated in myocardial tissues after myocardial I/R injury and inhibit cardiomyocyte apoptosis [8], whereas miR-208 was found to be upregulated in H9C2 cardiomyocytes after simulated I/R injury and promote cell apoptosis [9]. These results suggest that myocardial I/R injury is closely related to abnormal miRNA expression.…”

“…Increasing evidence suggests that miRNAs are associated with the occurrence and development of cardiovascular diseases by targeting different genes. For example, miR-497 was shown to suppress apoptosis and promote the proliferation of I/R-induced cardiomyocytes by targeting Mfn2 [8], while miR-208a enhanced the apoptosis of I/R-induced cardiomyocytes by targeting CHD9 [9]. Additionally, miR-378 was found to be downregulated during the hypertrophic growth of the heart and heart failure [10], while its upregulation attenuated cardiac hypertrophy and improved cardiac function by targeting MAPK1, IGF1R, GRB2, and KSR1 [11].…”

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

“…To further investigate the underlying mechanisms of miR-208a-3p-mediated regulation of OS progression, the downstream targets of miR-208a-3p were examined. Several genes have been identified to be directly targeted by miR-208a-3p, including SFRP1, cadherin 9 and thyroid hormone receptor associated protein 1 ( 19 , 34 , 35 ). The present study verified that PTEN was a direct target of miR-208a-3p in OS cells.…”

MicroRNA‑98‑5p prevents bone regeneration by targeting high mobility group AT‑Hook 2

“…It has been demonstrated that miRNAs serve a key role in a variety of biological processes, including cell proliferation, apoptosis and differentiation (2)(3)(4)(5). The abnormal expression of miRNA is associated with the development and progression of a variety of diseases including cancer, cardiovascular, metabolic, neurological and bone associated diseases (6)(7)(8)(9)(10)(11).…”