LncRNA MALAT1 regulates smooth muscle cell phenotype switch via activation of autophagy

Abstract

// Tie-Feng Song 1, * , Li-Wen Huang 1, * , Ying Yuan 1 , Hui-qin Wang 1 , Hong-Peng He 1 , Wen-Jian Ma 1 , Li-Hong Huo 1 , Hao Zhou 1 , Nan Wang 1 and Tong-Cun Zhang 1, 2 1 Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P.R. China 2 Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430000, P.R. China * These authors contributed equally to this work Correspondence to: Tong-Cun Zhang, email: tony@tust.edu.cn Nan Wang, email: wn929@tust.edu.cn Keywords: vascular smooth muscle cells; MALAT1; phenotype switching; autophagy; miR142-3p Received: August 20, 2017      Accepted: November 14, 2017      Published: December 14, 2017 ABSTRACT Vascular smooth muscle cells (VSMCs), switching from a differentiated to a proliferative phenotype, contribute to various vascular diseases. However, the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 MALAT1 in the phenotype switching of VSMCs remains unclear. Here, we report that the knockdown of MALAT1 promotes the transformation of smooth muscle cells from a proliferative phenotype to a differentiated phenotype. MALAT1 knockdown inhibited cellular proliferation and migration, leading to significant cell cycle arrest in the G2 phase. MALAT1 was downregulated in bone morphogenetic protein-7 (BMP-7)-induced cellular differentiation, while MALAT1 was upregulated in platelet-derived growth factor-BB (PDGF-BB)-induced cellular proliferation. PDGF induced the transformation of smooth muscle cells into a proliferative phenotype accompanied by an increase in autophagy. The downregulation of MALAT1 attenuated PDGF-BB-induced proliferation and migration by inhibiting autophagy. MALAT1 could act as a competing endogenous RNA (ceRNA) to regulate autophagy-related 7 (ATG7) gene expression by sponging miR142-3p. The present study reveals a novel mechanism by which MALAT1 promotes the transformation of smooth muscle cells from contraction to synthetic phenotypes.