title: A novel long non-coding RNA, hypoxia-inducible factor-2α promoter upstream transcript, functions as an inhibitor of osteosarcoma stem cells in vitro.
abstract: Long non‑coding RNAs (lncRNAs) have recently been identified as novel modulators of malignant tumors. However, the function of lncRNAs in cancer stem cells (CSCs) remains to be elucidated. The present study aimed to investigate the regulating role of a novel lncRNA, hypoxia‑inducible factor‑2α (HIF‑2α) promoter upstream transcript (HIF2PUT), in osteosarcoma stem cells. The expression levels of HIF2PUT were assessed by quantitative polymerase chain reaction in 17 osteosarcoma tissue specimens, and the correlation between the expression of HIF2PUT and its host transcript‑HIF‑2α was determined. In functional experiments, HIF2PUT expression was knocked down by small interfering RNAs, or overexpressed by transfection with pcDNA‑HIF2PUT, in order to evaluate the effects of HIF2PUT on cell proliferation, migration, expression rate of osteosarcoma stem cell marker CD133, and stem sphere‑forming ability in MG63 cells. HIF2PUT expression levels were positively correlated with HIF‑2α in osteosarcoma tissues. Overexpression of HIF2PUT markedly inhibited cell proliferation and migration, decreased the percentage of CD133 expressing cells, and impaired the osteosarcoma stem sphere‑forming ability of the MG63 cells. Whereas, knockdown of HIF2PUT expression had the opposite effect. Furthermore, altering the expression of HIF2PUT resulted in a concomitant change to HIF‑2α mRNA expression. These results indicate that the lncRNA HIF2PUT may be a novel regulatory factor of osteosarcoma stem cells, which may exert its function partly by controlling HIF‑2α expression. Further studies regarding HIF2PUT may provide a novel therapeutic target of osteosarcoma in the future.
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, PLA No. 161 Center Hospital, Wuhan, Hubei 430000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Haoye
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Oncology, PLA No. 161 Center Hospital, Wuhan, Hubei 430000, P.R. China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Oncology, PLA No. 161 Center Hospital, Wuhan, Hubei 430000, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Kunming General Hospital of Chendu Military Command, Kunming, Yunnan 650032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Aiyuan
authors.initials: A
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D055815:Young Adult; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D000099162:Endothelial PAS Domain-Containing Protein 1