Long non-coding RNA HAND2-AS1 downregulation predicts poor survival of patients with end-stage dilated cardiomyopathy

Abstract

Objective: Insulin-like growth factor-1 (IGF-1) signaling is inhibited in end-stage dilated cardiomyopathy (DCM), and recombinant IGF-1 improves cardiac function in DCM patients. Long non-coding (lnc)RNA HAND2-AS1 was previously shown to be involved in cancer development, but its role in DCM is unknown. The present study investigated the involvement of IGF-1 and HAND2-AS1 in DCM. Methods: Plasma HAND2-AS1 was detected by quantitative real-time PCR. IGF-1 plasma levels were measured by a human IGF-1 enzyme-linked immunosorbent assay. All experiments were performed in triplicate. Pearson’s correlation coefficient analyzed correlations between levels of IGF-1 and HAND2-AS1. Patients were divided into high and low IGF-1 or lncRNA HAND2-AS1 groups, and survival curves were plotted and compared by the Kaplan–Meier method and log-rank test, respectively. Results: Plasma levels of IGF-1 and lncRNA HAND2-AS1 were significantly lower in end-stage DCM patients than in healthy controls, and were only positively correlated in end-stage DCM patients. A follow-up study revealed that low levels of IGF-1 or lncRNA HAND2-AS1 were significantly associated with poor survival. In the human cardiomyocyte cell line AC16, lncRNA HAND2-AS1 overexpression failed to alter IGF-1 levels and IGF-1 overexpression did not affect lncRNA HAND2-AS1 expression. Conclusions: LncRNA HAND2-AS1 may participate in end-stage dilated cardiomyopathy.