MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A

// Wei Luo 1 , Hongbo He 1 , Wenfeng Xiao 1 , Qing Liu 1 , Zhenhan Deng 1 , Yaojuan Lu 2 , Qian Wang 2 , Qiping Zheng 2 , Yusheng Li 1 1 Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China 2 Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China Correspondence to: Yusheng Li, email: lys0209@163.com Qiping Zheng, email: qp_zheng@hotmail.com Keywords: IncRNA, MALAT1, MIR376A, osteosarcoma, TGFA Received: May 25, 2016 Accepted: July 08, 2016 Published: July 21, 2016 ABSTRACT Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) is a long non-coding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). Here, we showed that MALAT1 was increased in human OS cell lines and tissues and promoted OS cell growth, while MALAT1 knockdown suppressed OS cell growth. We also detected downregulation of MIR376A , a suppressor of OS growth, and upregulation of TGFA , a promoter of OS growth, in OS tissues. TGFA expression was positively correlated with MALAT1 expression, and both were negatively correlated with MIR376A expression. There was a direct interaction between MIR376A and MALAT1 via a putative MIR376A binding site within the MALAT1 3’-untranslated region (3’-UTR). There was also a direct interaction between MIR376A and the TGFA 3’-UTR. Thus, MALAT1 may promote OS cell growth through inhibition of MIR376A , leading to increased expression of TGFA . Our results suggest a MALAT1/MIR376A/TGFA axis mediates OS cell proliferation and tumor progression.