title: MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A.
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.
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Zhenhan
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Yaojuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C557041:MALAT1 long non-coding RNA, human; C573498:MIRN376C microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C587886:TGFA protein, human; D016211:Transforming Growth Factor alpha
keywords: IncRNA; MALAT1; MIR376A; TGFA; osteosarcoma