title: Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression.
abstract: Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China. xiechuuhai@sina.com.
authors.forename: Chu-Hai
authors.initials: CH
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Cao
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Qun-Wei
authors.initials: QW
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Zi-Wen
authors.initials: ZW
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Ju-Gen
authors.initials: JG
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Bin-Wei
authors.initials: BW
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Chang-gang-dong Road, Guangzhou, 510260, China.
authors.forename: Bo-Yi
authors.initials: BY
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C000598536:TUG1 long noncoding RNA, human
keywords: Osteosarcoma; POU2F1; TUG1; ceRNA; miR-9-5p