Silencing TTTY15 mitigates hypoxia-induced mitochondrial energy metabolism dysfunction and cardiomyocytes apoptosis via TTTY15/let-7i-5p and TLR3/NF-κB pathways.

Noncoding RNAs are interweaved in pathological processes in myocardial ischemia (MI), such as long noncoding RNA (lncRNA) and microRNAs (miRNAs). The aim of this study was to figure out the role of Testis-specific transcript Y-linked 15 (TTTY15) and let-7i-5p in cell model of MI in cardiomyocytes. Hypoxia-induced cell injury was assessed by Cell counting kit 8 assay, flow cytometry, commercial kits and western blotting. As a result, hypoxia stress induced inhibition on cell proliferation, glucose uptake, and ATP production, and promotion on apoptosis, lactate dehydrogenase (LDH) release, and lactic acid production in human cardiomyocyte AC16 cells. During hypoxia injury, expression of TTTY15 and let-7i-5p was measured by real-time quantitative polymerase chain reaction, and TTTY15 was upregulated, accompanied with let-7i-5p downregulation. Functionally, either silencing TTTY15 or overexpressing let-7i-5p could attenuate hypoxia-induced apoptosis and mitochondrial energy metabolism dysfunction in AC16 cells. Moreover, there was an interaction between TTTY15 and let-7i-5p via target binding, as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Knockdown of let-7i-5p could counteract the protective role of TTTY15 deletion in hypoxic AC16 cells. Meanwhile, toll-like receptor 3 (TLR3)/nuclear factor-kappa B (NF-κB) signaling was validated by western blotting. Expression of TLR3, tumor necrosis factor receptor-associated factor 6 (TRAF6) and phosphorylated p65 was promoted in hypoxic AC16 cells, which was abrogated by TTTY15 silencing along with let-7i-5p upregulation. Collectively, TTTY15 knockdown protects cardiomyocytes against hypoxia-induced apoptosis and mitochondrial energy metabolism dysfunction in vitro through let-7i-5p/TLR3/NF-κB pathway to suppress.