title: MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1.
abstract: Metastasis is a leading cause of mortality for osteosarcoma patients. The molecular pathological mechanism remains to be elucidated. In the previously study, we established two osteosarcoma cell lines with different metastatic potentials. Differential expressed genes and proteins regarding metastatic ability have been identified. MicroRNAs are important regulators in tumorigenesis and tumor progression. In this study, microRNA microarray was used to assess the differential expressed miRNAs level between these two cell lines. One of the top ranked miRNAs-miR-195 was identified highly expressing in lowly metastatic cells. It was showed that over-expression of miR-195 substantially inhibits migration and invasion of osteosarcoma cells in vitro and pulmonary metastasis formation in vivo. Meanwhile, CCND1 was identified as the target gene of miR-195 and further studied. More importantly, using real-time PCR, we evaluated the expression of miR-195 and CCND1 in osteosarcoma samples from 107 frozen biopsy tissues and 99 formalin- or paraformalin-fixed, paraffin-embedded (FFPE) tissues. Results indicated lowly expressed miR-195 or highly CCND1 correlated with positive overall survival and their expression inversely related to each other. In summary, our study suggests miR-195 functions as a tumor metastasis suppressor gene by down-regulating CCND1 and can be used as a potential target in the treatment of osteosarcoma.
authors.affiliation: Department of Spinal Cord Injury, General Hospital of Jinan Military Area Command of Chinese PLA, Jinan, Shandong, People's Republic of China.|Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Bian
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Baoan
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Tongtao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Chengkui
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: QingYu
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Spinal Cord Injury, General Hospital of Jinan Military Area Command of Chinese PLA, Jinan, Shandong, People's Republic of China.
authors.forename: Ting Bao
authors.initials: TB
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor / Q000637:transplantation; D002465:Cell Movement; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D016016:Proportional Hazards Models; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C530104:CCND1 protein, human; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D019938:Cyclin D1
keywords: CCND1; metastatic; miR-195; microRNA; osteosarcoma
references.citation: Nat Rev Genet. 2004 Jul;5(7):522-31
references.pmid: 15211354
references.citation: Cell. 2007 Jun 29;129(7):1401-14
references.pmid: 17604727
references.citation: Hepatology. 2009 Jul;50(1):113-21
references.pmid: 19441017
references.citation: Endocrinology. 2004 Dec;145(12):5439-47
references.pmid: 15331580
references.citation: Cancer Biol Ther. 2011 Jan 15;11(2):287-92
references.pmid: 21079421
references.citation: Med Oncol. 2012 Jun;29(2):919-27
references.pmid: 21390519
references.citation: J Clin Oncol. 2005 Jun 20;23(18):4215-24
references.pmid: 15961768
references.citation: Curr Opin Struct Biol. 2005 Jun;15(3):331-41
references.pmid: 15925505
references.citation: Cancer. 2009 Apr 1;115(7):1531-43
references.pmid: 19197972
references.citation: RNA. 2012 Sep;18(9):1635-55
references.pmid: 22850425
references.citation: J Biol Chem. 2005 Apr 29;280(17):16934-41
references.pmid: 15713663
references.citation: Cancer Res. 1986 Aug;46(8):4109-15
references.pmid: 3731078
references.citation: Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
references.pmid: 15852042
references.citation: J Biol Chem. 2010 Jun 4;285(23):17869-79
references.pmid: 20371610
references.citation: Mol Carcinog. 2014 Feb;53(2):138-44
references.pmid: 22949271
references.citation: Hepatology. 2013 Aug;58(2):642-53
references.pmid: 23468064
references.citation: PLoS One. 2013;8(1):e53906
references.pmid: 23372675
references.citation: Am J Pathol. 1997 Jul;151(1):161-8
references.pmid: 9212742
references.citation: Am J Pathol. 1997 Feb;150(2):705-11
references.pmid: 9033283
references.citation: Braz J Med Biol Res. 2007 Nov;40(11):1435-40
references.pmid: 17934639
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Mol Ther. 2011 Jun;19(6):1123-30
references.pmid: 21427707
references.citation: RNA. 2003 Feb;9(2):175-9
references.pmid: 12554859
references.citation: Br J Pharmacol. 2011 Feb;162(3):688-700
references.pmid: 20942814
references.citation: Cancer Treat Rev. 2014 May;40(4):523-32
references.pmid: 24345772
references.citation: Paediatr Drugs. 2008;10(5):315-27
references.pmid: 18754698
references.citation: Cytotechnology. 2009 Nov;61(1-2):37-44
references.pmid: 20016965
references.citation: Clin Cancer Res. 2009 Dec 15;15(24):7684-7692
references.pmid: 19996210
references.citation: Oncogene. 2013 Jun 27;32(26):3175-83
references.pmid: 22847610
references.citation: Int J Cancer. 1989 Jul 15;44(1):131-6
references.pmid: 2744882
references.citation: Cell. 2001 Dec 28;107(7):823-6
references.pmid: 11779458
references.citation: Cell Cycle. 2006 Nov 1;5(21):2440-2
references.pmid: 17106256
references.citation: Mayo Clin Proc. 2012 May;87(5):475-87
references.pmid: 22560526