MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway.
Bioinformatics analysis showed that miR-448-5p expression in the myocardial tissue of rats with myocardial infarction significantly increased, suggesting that it may participate in myocardial cell apoptosis in myocardial infarction. This study aimed to explore the protective effects of miR-448-5p on hypoxic myocardial cells.H9C2 cells were cultured and subjected to anoxia for 2, 4, and 8 hours to establish a hypoxia model. MiR-448-5p mimic and inhibitor were transfected into the cells; then, a dual-luciferase experiment was conducted to verify the targeting relationship between miR-448-5p and VEGFA. Cell viability and apoptosis was detected by cell counting kit-8 and ﬂow cytometry, respectively. The expressions of apoptosis-related proteins, miR-448-5p, FAS, and FAS-L were measured using western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Hypoxia-reduced H9C2 cell viability and promoted apoptosis. MiR-448-5p expression was increased after H9C2 cell hypoxia. MiR-448-5p mimic significantly inhibited the viability and promoted the apoptosis of hypoxia-induced model cells. Hypoxia promoted the expression of apoptosis-related protein B-cell lymphoma-2 (Bcl-2) and inhibited the expressions of Bcl-2-associated x protein (Bax), cleaved caspase-3, and caspase-3, whereas the effect of inhibitor on hypoxia-reduced H9C2 cell and apoptotic protein expression were opposite to miR-448-5p mimic. MiR-448-5p targeted VEGFA and regulated its expression. Silenced VEGFA expression significantly inhibited inhibitor effect on increasing cell viability and promoted apoptosis. In addition, miR-448-5p mimic inhibited the effect of hypoxia on promoting the expressions of FAS and FAS-L of H9C2 cells. Inhibitors had the opposite effect on cell hypoxia model.The miR-448-5p/VEGFA axis could protect cardiomyocytes from hypoxia through inhibiting the FAS/FAS-L signaling pathway.
['Tang|Hanqing|H|', 'Zhang|Shitian|S|', 'Huang|Cenhan|C|', 'Li|Keming|K|', 'Zhao|Qiuhua|Q|', 'Li|Xiaohua|X|']
D000818:Animals D017209:Apoptosis D002460:Cell Line D053222:Fas Ligand Protein D000860:Hypoxia D035683:MicroRNAs D032383:Myocytes, Cardiac D051381:Rats D015398:Signal Transduction D042461:Vascular Endothelial Growth Factor A D019014:fas Receptor
Cell viability Hypdoxia injury