title: miR-214 promotes the proliferation and invasion of osteosarcoma cells through direct suppression of LZTS1.
abstract: Previous studies have shown that miR-214 functions either as an oncogene or a tumor suppressor in various human cancer types. The role of this microRNA in osteosarcoma (OS) is presently unclear. Here, we demonstrated that miR-214 is frequently upregulated in OS specimens, compared with noncancerous bone tissues. Bioinformatics analysis further revealed leucine zipper, putative tumor suppressor 1 (LZTS1) as a potential target of miR-214. Expression patterns of miR-214 were inversely correlated with those of LZTS1 mRNA and protein in OS tissues. Data from reporter assays showed that miR-214 directly binds to the 3'-untranslated region (3'-UTR) of LZTS1 mRNA and suppresses expression at both transcriptional and translational levels. In functional assays, miR-214 promoted OS cell proliferation, invasion and tumor growth in nude mice, which could be reversed by overexpression of LZTS1. Taken together, our data provide compelling evidence that miR-214 functions as an onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of LZTS1.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: wangtaohappy2010@sohu.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C118711:LZTS1 protein, human; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins
keywords: LZTS1; Osteosarcoma; miR-214