Downregulated long noncoding RNA LUCAT1 inhibited proliferation and promoted apoptosis of cardiomyocyte via miR-612/HOXA13 pathway in chronic heart failure

Objective Long non-coding RNAs (lncRNAs) have been reported to play important roles in numerous kinds of cardiovascular disease, including chronic heart failure (CHF). In this study, we mainly focused on investigating the potential roles of lncRNA LUCAT1 patients with CHF. Patients and methods RT-PCR was used to detect the expressions of LUCAT1 and miR-612 in serum samples of CHF patients (n=60) and healthy volunteers. Relationships between the expressions of LUCAT1 and miR-612, LUCAT1 and overall survival (OS) were analyzed using the Kaplan-Meier method. Si-LUCAT1 and miR-612 mimic were constructed and respectively transfected into AC16 cells to explore the functions of LUCAT1 and miR-612. Cell proliferation abilities were detected by CCK-8 assay AC16 cells. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect the protein levels of HOXA13, Bcl-2, Bax, Bad and Cleaved Caspase3. In addition, luciferase gene reporter assay was used to prove the relationships between LUCAT1 and miR-612, miR-612 and HOXA13. Results Firstly, we found that LUCAT1 was decreased for 1.7 folds in CHF patients, which was correlated with poor prognosis patients. LUCAT1 repression inhibited cell proliferation and promoted cell apoptosis in human cardiomyocyte cell line AC16 cells. Furthermore, we found that miR-612 was increased for 2.0 folds in CHF patients, which was negatively interacted with LUCAT1 expression. Luciferase gene reporter assay demonstrated that LUCAT1 could directly bind with miR-612 in AC16 cells. Moreover, miR-612 overexpression also inhibited cell proliferation and promoted cell apoptosis in AC16 cells. Luciferase reporter assay indicated that miR-612 could directly target at HOXA13 in AC16 cells, which was associated with cell proliferation and apoptosis. Finally, miR-612 inhibitor was transfected into AC16 cells with si-LUCAT1. The results showed that the inhibited cell proliferation and promoted cell apoptosis were reversed, which confirmed that LUCAT1 repression inhibited cell proliferation and promoted apoptosis via miR-612/HOXA13 axis in CHF patients. Conclusions According to the above results, our study revealed that LUCAT1 was decreased in CHF patients, which was correlated with poor prognosis of CHF patients. Furthermore, the downregulation of LUCAT1 inhibited cell proliferation and promoted cell apoptosis via targeting miR-612/HOXA13 axis. Our results elucidated a potential mechanism underlying cardiomyocyte apoptosis, which might be used as a promising prognostic marker and a potential target for CHF patients.