title: MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p.
abstract: Recently, emerging evidence has demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNAs (lncRNAs), contributes to the initiation and development of tumors, including osteosarcoma (OS). Multiple studies have suggested an oncogenic role of MALAT1 and high-mobility group protein B1 (HMGB1) in OS tumorigenesis and metastasis, but the effects and mechanisms are not unanimous. Here, we showed that MALAT1 and HMGB1 were significantly increased in human OS cell lines and knockdown of MALAT1 reduced HMGB1 expression. By using online tools, we screen out 2 candidate miRNAs, miR-142-3p and miR-129-5p which may be associated with both MALAT1 and HMGB1. Luciferase reporter assay revealed a direct interaction between the 2 miRNAs and MALAT1, respectively, via a putative binding site within MALAT1. Meanwhile, both the 2 miRNAs could bind to HMGB1 3'-untranslated region (3'-UTR) and regulate HMGB1 expression. Moreover, knockdown of MALAT1 decreased HMGB1 expression, inhibited OS cell growth and promoted apoptosis, while miR-142-3p and miR-129-5p inhibitor partly restored the inhibitory effect of MALAT1 knockdown on HMGB1 expression, OS cell growth and the promotion of apoptosis. In OS tissues, the expression of MALAT1 and HMGB1 was upregulated while the expression of miR-142-3p and miR-129-5p was downregulated. Together, our results support a MALAT1/miR-142-3p/miR-129-5p/HMGB1 axis in OS cell proliferation and tumor progression. MALAT1 promoted OS cell growth through inhibition of miR-142-3p or miR-129-5p and by targeting HMGB1.
authors.affiliation: a Department of Ophthalmology , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Ni
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Deye
authors.initials: D
authors.lastname: Song
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Muliang
authors.initials: M
authors.lastname: Ding
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Xianzhe
authors.initials: X
authors.lastname: Huang
authors.affiliation: b Department of Orthopaedics , The Second Xiangya Hospital, Central South University , Changsha , Hunan , P.R. China.
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001859:Bone Neoplasms / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D024243:HMGB1 Protein; C557041:MALAT1 long non-coding RNA, human; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D062085:RNA, Long Noncoding
keywords: HMGB1; lncRNA-MALAT1; miR-129–5p; miR-142–3p; osteosarcoma