MiR-532-3p Suppresses Nucleus Pulposus Cells Proliferation and Extracellular Matrix Production, Promotes Cell Apoptosis via Targeting High Mobility Group AT-Hook 2

Abstract

The present study aimed to investigate the function and mechanism of microRNA (miR)-532-3p in intervertebral disc degeneration (IDD). Further, whether miR-532-3p regulates HMGA2 in nucleus pulposus (NP) cells was explored. We collected human nucleus pulposus (NP) tissues from the patients with IDD, and detected miR-532-3p in NP tissues using RT-qPCR. MiR-532-3p mimic and inhibitor were constructed, and they were transfected into the human nucleus pulposus cells (HNPCs) by Lipofectamine 3000. MTT assay was conducted to determine cell proliferation. Cell apoptosis and extracellular matrix remodeling were examined by flow cytometric, Caspase 3/8 Assay Kits and Western blot. A dual-luciferase reporter assay was applied to investigate whether miR-532-3p targets High mobility group AT-hook 2 (HMGA2). We found miR-532-3p expression level was significantly increased in NP tissues of IDD patients, comparing with the controls. MiR-532-3p exerted an inhibitory effect on HNPCs proliferation; however, cell apoptosis and the degradation of extracellular matrix were induced by miR-532-3p. MiR-532-3p directly targets HMGA2, and HMGA2 overexpression reversed the role of miR-532-3p mimic in HNPCs proliferation, apoptosis, and extracellular matrix remodeling. Our study is the first to report that miR-532-3p might suppress NP cell proliferation, promote cell apoptosis and inhibit ECM production of NP cells via targeting HMGA2, thus facilitating the progression of IDD. MiR-532-3p was supposed to be a novel target for the treatment of IDD.