LncRNA HOXA-AS2 accelerates the proliferation and migration and inhibits the apoptosis of vascular smooth muscle cells by absorbing miRNA-877-3p

T.-T. Fan, Y.-X. Liu, X.-C. Wang, B.-L. Xu, Z.-C. Chen, H.-A. Lu, M. Zhang

Department of Cardiovascular Medicine, The Second Hospital of Anhui Medical University, Hefei, China. tozpha@163.com

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• Cardiology

OBJECTIVE: The aim of this study was to clarify the role of long non-coding RNA (lncRNA) HOXA-AS2 in influencing the proliferative, migratory and apoptotic abilities of human aortic vascular smooth muscle cells (HA-VSMCs) by absorbing microRNA-877-3p (miRNA-877-3p).

MATERIALS AND METHODS: HOXA-AS2 level in HA-VSMCs treated with different doses of oxidized low-density lipoprotein (ox-LDL) and for different time points was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After transfection of si-HOXA-AS2 in HA-VSMCs undergoing ox-LDL treatment, the viability, apoptotic rate and migration of cells were detected, respectively. Meanwhile, the subcellular distribution of HOXA-AS2 was analyzed. The Dual-Luciferase reporter gene assay was applied to verify the binding relationship between HOXA-AS2 and miRNA-877-3p. MiRNA-877-3p level in HA-VSMCs treated with different doses of ox-LDL was determined as well. Furthermore, the regulatory effects of HOXA-AS2/miRNA-877-3p axis on cellular behaviors of HA-VSMCs were determined.

RESULTS: HOXA-AS2 expression was upregulated by ox-LDL treatment in a time- and dose-dependent manner. After being treated with 100 mg/L ox-LDL for 48 h, the proliferative and migratory abilities of HA-VSMCs were significantly enhanced, while apoptosis was inhibited. Conversely, these changes were reversed by transfection of si-HOXA-AS2. HOXA-AS2 was mainly distributed in the nuclear fraction. Dual-Luciferase reporter gene assay confirmed the direct binding relationship between HOXA-AS2 and miRNA-877-3p. Moreover, miRNA-877-3p was markedly downregulated after transfection of si-HOXA-AS2. MiRNA-877-3p expression decreased gradually with an increased dose of ox-LDL. In addition, knockdown of miRNA-877-3p could reverse the regulatory effects of HOXA-AS2 on proliferative, migratory and apoptotic abilities of HA-VSMCs.

CONCLUSIONS: HOXA-AS2 is upregulated after HA-VSMCs injury, which accelerates the proliferative and migratory abilities, and inhibits the apoptosis of vascular smooth muscle cells by absorbing miRNA-877-3p.

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