title: miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell             cycle arrest in osteosarcoma.
abstract: Osteosarcoma, the most common primary tumor of the bones, causes many deaths due to its rapid proliferation and drug resistance. Recent studies have shown that cyclin D1 plays a key regulatory role during cell proliferation, and non-coding microRNAs (miRNAs) act as crucial modulators of cyclin D1 (CCND1). The aim of the current study was to determine the role of miRNAs in controlling CCND1 expression and inducing cell apoptosis. CCND1 has been found to be a target of miR-15a and miR-16-1 through analysis of complementary sequences between microRNAs and CCND1 mRNA. The upregulation of miR-15a and miR-16-1 in the cell line SOSP-9607 induces apoptosis and cell cycle arrest. Osteosarcoma cells transfected with miR-15a and miR-16-1 show slower proliferation curves. Moreover, the transcription of CCND1 is suppressed by miR-15a and miR-16-1 via direct binding to the CCND1 3'-untranslated region (3'-UTR). The data presented here demonstrate that the CCND1 contributes to osteosarcoma cell proliferation, suggesting that repression of CCND1 by miR-15a and miR-16-1 could be used for osteosarcoma therapy.
authors.affiliation: Department of Orthopedic Surgery Center and Orthopedic Oncology Institute of People's Liberation Army, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: Cheng-Kui
authors.initials: CK
authors.lastname: Cai
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Zhao
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Tian
authors.forename: Lie
authors.initials: L
authors.lastname: Liu
authors.forename: Kang
authors.initials: K
authors.lastname: Yan
authors.forename: Yun-Lei
authors.initials: YL
authors.lastname: Ma
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Ji
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Li
authors.forename: Kang
authors.initials: K
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Xiu-Chun
authors.initials: XC
authors.lastname: Qiu
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Fan
authors.forename: Tong-Tao
authors.initials: TT
authors.lastname: Yang
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C530104:CCND1 protein, human; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1