Regulation of laryngeal squamous cell cancer progression by the lncRNA H19/miR-148a-3p/DNMT1 axis

// Tianyi Wu 1, * , Lingmei Qu 2, * , Guoqing He 1, * , Linli Tian 1, * , Liang Li 1 , Han Zhou 1 , Qian Jin 1 , Jingyuan Ren 3 , Yu Wang 1 , Jingting Wang 1 , Xuan Kan 1 , Ming Liu 1 , Jia Shen 4 , Mian Guo 5 , Yanan Sun 1 1 Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China 3 Department of Head and Neck Surgery, The Oncology Hospital of Jilin province, Changchun, China 4 Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA 5 Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China * These authors contributed equally to this work Correspondence to: Yanan Sun, e-mail: 76202920@qq.com Mian Guo, e-mail: guomian_hyd@163.com Keywords: laryngeal squamous cell cancer, lncRNA H19, miR-148a-3p, DNMT1 Received: July 07, 2015      Accepted: December 05, 2015      Published: February 08, 2016 ABSTRACT Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer. The regulation of LSCC progression by long non-coding RNA (lncRNA) was not well understood. In this study, we reported that the lncRNA H19 was upregulated in LSCC. The expression levels of H19 were inversely correlated with the survival rate of LSCC patients. Knockdown of H19 expression inhibited LSCC cell migration, invasion and proliferation. We identified microRNA miR-148a-3p as an inhibitory target for H19. Overexpression of miR-148a-3p reduced LSCC migration, invasion and proliferation cell, while inhibition of miR-148a-3p did the opposite. The inhibition of LSCC progression induced by H19 knockdown required the activity of miR-148a-3p. We also identified DNA methyltransferase enzyme DNMT1 as a target of miR-148a-3p. Cellular DNA methylation levels were inhibited by both miR-148a-3p overexpression and H19 knockdown. In summary, our study demonstrated that the lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1.