title: MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6.
abstract: Osteosarcoma is the most common primary sarcoma of bone, and it is a leading cause of cancer death among adolescents and young adults. However, the molecular mechanism underlying osteosarcoma carcinogenesis remains poorly understood. Recently, cyclin-dependent kinase 6 (CDK6) was identified as an important oncogene. We found that CDK6 protein level, rather than CDK6 mRNA level, is much higher in osteosarcoma tissues than in normal adjacent tissues, which indicates a post-transcriptional mechanism involved in CDK6 regulation in osteosarcoma. MiRNAs are small non-coding RNAs that repress gene expression at the post-transcriptional level and have widely been shown to play important roles in many human cancers. In this study, we investigated the role of miR-29b as a novel regulator of CDK6 using bioinformatics methods. We demonstrated that CDK6 can be downregulated by miR-29b via binding to the 3'-UTR region in osteosarcoma cells. Furthermore, we identified an inverse correlation between miR-29b and CDK6 protein levels in osteosarcoma tissues. Finally, we examined the function of miR-29b-driven repression of CDK6 expression in osteosarcoma cells. The results revealed that miR-29b acts as a tumor suppressor of osteosarcoma by targeting CDK6 in the proliferation and migration processes. Taken together, our results highlight an important role for miR-29b in the regulation of CDK6 in osteosarcoma and may open new avenues for future osteosarcoma therapies.
authors.affiliation: Department of Orthopedics, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, 210002, China.|State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Kegan
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, 210002, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Orthopedics, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, 210002, China.
authors.forename: Gentao
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210046, China. cyzhang@nju.edu.cn.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210046, China. xichen@nju.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, 210002, China. oxis@163.com.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051361:Cyclin-Dependent Kinase 6
keywords: miR-29b; migration; osteosarcoma; proliferation; tumorigenesis