Long noncoding RNA ILF3-AS1 regulates myocardial infarction via the miR-212-3p/SIRT1 axis and PI3K/Akt signaling pathway.

OBJECTIVE

Myocardial infarction (MI) is a serious cardiac disease due to its high incidence and mortality worldwide. Long noncoding RNAs (lncRNAs) have been found to play an essential role in the pathological progress of various cardiovascular diseases. ILF3-AS1 is a newly identified lncRNA, and many studies have demonstrated that ILF3-AS1 affects the development of various malignancies. However, the biological function of ILF3-AS1 and its underlying mechanism in MI are still unknown. In the present study, the function of ILF3-AS1 and the possible mechanisms against hypoxia-induced apoptosis in H9c2 cells were investigated.

MATERIALS AND METHODS

H9c2 cells were exposed to hypoxia (1% O2) to mimic the in vitro model of MI. The levels of lncRNA ILF3-AS1 and microRNA miR-212-3p were measured by real-time PCR (RT-PCR). Transfection was performed to upregulate the levels of ILF3-AS1 and miR-212-3p. Western blot assays were carried out to measure protein expression. The relationship between ILF3-AS1 and miR-212-3p was verified by Dual-Luciferase reporter assay.

RESULTS

We found that ILF3-AS1 was downregulated by hypoxia. Overexpression of ILF3-AS1 resulted in the relief of hypoxia-induced damage to H9c2 cells by rescuing cell viability, migration, and invasion and suppressing apoptosis, while downregulation of ILF3-AS1 had the opposite effects. Moreover, ILF3-AS1 could negatively regulate miR-212-3p expression, and upregulation of ILF3-AS1 could alleviate hypoxic injury via downregulation of miR-212-3p. Moreover, miR-212-3p negatively regulated SIRT1 expression. Further investigations revealed that ILF3-AS1 activated PI3K/Akt signaling and that application of the PI3K inhibitor LY294002 could abrogate the protective effects of ILF3-AS1 against hypoxia.

CONCLUSIONS

In summary, we concluded that ILF3-AS1 provides protection against hypoxia-induced injury via the PI3K/Akt pathway, which may provide clues for the treatment of patients with MI.