MicroRNAs and Potential Targets in Osteosarcoma: Review

Frontiers in Pediatrics

Volumn 3, Issue , 2015, Pages

  Sampson, Valerie B ^a   Yoo, Soonmoon ^a   Kumar, Asmita ^a   Vetter, Nancy S ^a   Kolb, E Anders ^a  

^a NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

Author keywords

apoptosis; cell proliferation; microRNA; mutations; osteosarcoma

Indexed keywords

EID: 85009856515     PISSN: None     EISSN: 22962360     Source Type: Journal    
DOI: 10.3389/fped.2015.00069     Document Type: Review

References (131)

1. Vander Griend RA. Osteosarcoma and its variants. Orthop Clin North Am (1996) 27(3):575–81.8649738
2. Overholtzer M Rao PH Favis R Lu XY Elowitz MB Barany F et al. The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc Natl Acad Sci U S A (2003) 100(20):11547–52.10.1073/pnas.193485210012972634
3. Mohseny AB Szuhai K Romeo S Buddingh EP Briaire-de Bruijn I de Jong D et al. Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol (2009) 219(3):294–305.10.1002/path.260319718709
4. Ottaviani G Jaffe N. The etiology of osteosarcoma. Cancer Treat Res (2009) 152:15–32.10.1007/978-1-4419-0284-9_220213384
5. Fagioli F Aglietta M Tienghi A Ferrari S Brach del Prever A Vassallo E et al. High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study. J Clin Oncol (2002) 20(8):2150–6.10.1200/JCO.2002.08.08111956277
6. Fire A Xu S Montgomery MK Kostas SA Driver SE Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature (1998) 391(6669):806–11.10.1038/358889486653
7. Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev (2015) 87:3–14.10.1016/j.addr.2015.05.001
8. Calin GA Sevignani C Dumitru CD Hyslop T Noch E Yendamuri S et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A (2004) 101(9):2999–3004.10.1073/pnas.030732310114973191
9. Gao J Yang TT Qiu XC Yu B Han JW Fan QY et al. [Cloning and identification of microRNA from human osteosarcoma cell line SOSP-9607]. Ai Zheng (2007) 26(6):561–5.17562257
10. Maire G Martin JW Yoshimoto M Chilton-MacNeill S Zielenska M Squire JA. Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet (2011) 204(3):138–46.10.1016/j.cancergen.2010.12.01221504713
11. Lulla RR Costa FF Bischof JM Chou PM de F Bonaldo M Vanin EF et al. Identification of differentially expressed microRNAs in osteosarcoma. Sarcoma (2011) 2011:732690.10.1155/2011/73269021789031
12. Moriarity BS Otto GM Rahrmann EP Rathe SK Wolf NK Weg MT et al. A sleeping beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis. Nat Genet (2015) 47(6):615–24.10.1038/ng.329325961939
13. Mogilyansky E Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ (2013) 20(12):1603–14.10.1038/cdd.2013.12524212931
14. Aqeilan RI Calin GA Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ (2010) 17(2):215–20.10.1038/cdd.2009.6919498445
15. Sampson VB Rong NH Han J Yang Q Aris V Soteropoulos P et al. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res (2007) 67(20):9762–70.10.1158/0008-5472.CAN-07-246217942906
16. Chou AJ Gorlick R. Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther (2006) 6(7):1075–85.10.1586/14737140.6.7.107516831079
17. Poos K Smida J Nathrath M Maugg D Baumhoer D Neumann A et al. Structuring osteosarcoma knowledge: an osteosarcoma-gene association database based on literature mining and manual annotation. Database (Oxford) (2014) 2014:bau042.10.1093/database/bau04224865352
18. Sarver AL Thayanithy V Scott MC Cleton-Jansen AM Hogendoorn PC Modiano JF et al. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma. Orphanet J Rare Dis (2013) 8:7.10.1186/1750-1172-8-723311495
19. Squire JA Pei J Marrano P Beheshti B Bayani J Lim G et al. High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer (2003) 38(3):215–25.10.1002/gcc.1027314506695
20. Lau CC Harris CP Lu XY Perlaky L Gogineni S Chintagumpala M et al. Frequent amplification and rearrangement of chromosomal bands 6p12-p21 and 17p11.2 in osteosarcoma. Genes Chromosomes Cancer (2004) 39(1):11–21.10.1002/gcc.1029114603437
21. Bridge JA Nelson M McComb E McGuire MH Rosenthal H Vergara G et al. Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature. Cancer Genet Cytogenet (1997) 95(1):74–87.10.1016/S0165-4608(96)00306-89140456
22. Fang ZH Han ZC. The transcription factor E2F: a crucial switch in the control of homeostasis and tumorigenesis. Histol Histopathol (2006) 21(4):403–13.16437386
23. Friend SH Bernards R Rogelj S Weinberg RA Rapaport JM Albert DM et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature (1986) 323(6089):643–6.10.1038/323643a02877398
24. Deshpande A Hinds PW. The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr Mol Med (2006) 6(7):809–17.10.2174/156652401060607080917100605
25. Mahalingam D Mita A Sankhala K Swords R Kelly K Giles F et al. Targeting sarcomas: novel biological agents and future perspectives. Curr Drug Targets (2009) 10(10):937–49.10.2174/13894500978957799019860642
26. Li M Lockwood W Zielenska M Northcott P Ra YS Bouffet E et al. Multiple CDK/CYCLIND genes are amplified in medulloblastoma and supratentorial primitive neuroectodermal brain tumor. Cancer Genet (2012) 205(5):220–31.10.1016/j.cancergen.2012.03.00222682621
27. Okamoto R Ogawa S Nowak D Kawamata N Akagi T Kato M et al. Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia. Haematologica (2010) 95(9):1481–8.10.3324/haematol.2009.01111420435627
28. Wadayama B Toguchida J Shimizu T Ishizaki K Sasaki MS Kotoura Y et al. Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res (1994) 54(11):3042–8.8187094
29. Toguchida J Ishizaki K Nakamura Y Sasaki MS Ikenaga M Kato M et al. Assignment of common allele loss in osteosarcoma to the subregion 17p13. Cancer Res (1989) 49(22):6247–51.2572320
30. Poos K Smida J Nathrath M Maugg D Baumhoer D Korsching E. How microRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation. PLoS Comput Biol (2013) 9(8):e1003210.10.1371/journal.pcbi.100321024009496
31. Osaki M Takeshita F Sugimoto Y Kosaka N Yamamoto Y Yoshioka Y et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther (2011) 19(6):1123–30.10.1038/mt.2011.5321427707
32. Feng M Yu Q. miR-449 regulates CDK-Rb-E2F1 through an auto-regulatory feedback circuit. Cell Cycle (2010) 9(2):213–4.10.4161/cc.9.2.10502
33. Yang X Feng M Jiang X Wu Z Li Z Aau M et al. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev (2009) 23(20):2388–93.10.1101/gad.181900919833767
34. Chen J Zhou J Chen X Yang B Wang D Yang P et al. miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2. Tumour Biol (2015).10.1007/s13277-015-3568-y26002578
35. Zhang W Qian JX Yi HL Yang ZD Wang CF Chen JY et al. The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression. Mol Biol (Mosk) (2012) 46(4):622–7.10.1134/S002689331204013923113351
36. Baumhoer D Zillmer S Unger K Rosemann M Atkinson MJ Irmler M et al. MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma. Cancer Genet (2012) 205(5):212–9.10.1016/j.cancergen.2012.03.00122682620
37. Namløs HM Meza-Zepeda LA Barøy T Østensen IH Kresse SH Kuijjer ML et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One (2012) 7(10):e48086.10.1371/journal.pone.004808623133552
38. Mejia-Guerrero S Quejada M Gokgoz N Gill M Parkes RK Wunder JS et al. Characterization of the 12q15 MDM2 and 12q13-14 CDK4 amplicons and clinical correlations in osteosarcoma. Genes Chromosomes Cancer (2010) 49(6):518–25.10.1002/gcc.2076120196171
39. Guo W Wang X Feng C. P53 gene abnormalities in osteosarcoma. Chin Med J (Engl) (1996) 109(10):752–5.
40. Momand J Jung D Wilczynski S Niland J. The MDM2 gene amplification database. Nucleic Acids Res (1998) 26(15):3453–9.10.1093/nar/26.15.34539671804
41. Jones M Lal A. MicroRNAs, wild-type and mutant p53: more questions than answers. RNA Biol (2012) 9(6):781–91.10.4161/rna.2014622664917
42. He L He X Lim LP de Stanchina E Xuan Z Liang Y et al. A microRNA component of the p53 tumour suppressor network. Nature (2007) 447(7148):1130–4.10.1038/nature0593917554337
43. Raver-Shapira N Marciano E Meiri E Spector Y Rosenfeld N Moskovits N et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell (2007) 26(5):731–43.10.1016/j.molcel.2007.05.01717540598
44. Lodygin D Tarasov V Epanchintsev A Berking C Knyazeva T Körner H et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle (2008) 7(16):2591–600.10.4161/cc.7.16.653318719384
45. He C Xiong J Xu X Lu W Liu L Xiao D et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun (2009) 388(1):35–40.10.1016/j.bbrc.2009.07.10119632201
46. van der Deen M Taipaleenmäki H Zhang Y Teplyuk NM Gupta A Cinghu S et al. MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem (2013) 288(29):21307–19.10.1074/jbc.M112.44589023720736
47. Pulikkan JA Peramangalam PS Dengler V Ho PA Preudhomme C Meshinchi S et al. C/EBPalpha regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood (2010) 116(25):5638–49.10.1182/blood-2010-04-28160020889924
48. Braun CJ Zhang X Savelyeva I Wolff S Moll UM Schepeler T et al. p53-responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res (2008) 68(24):10094–104.10.1158/0008-5472.CAN-08-156919074875
49. Wang Y Jia LS Yuan W Wu Z Wang HB Xu T et al. Low miR-34a and miR-192 are associated with unfavorable prognosis in patients suffering from osteosarcoma. Am J Transl Res (2015) 7(1):111–9.25755833
50. Song B Wang Y Titmus MA Botchkina G Formentini A Kornmann M et al. Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer (2010) 9:96.10.1186/1476-4598-9-9620433742
51. Martin JW Chilton-MacNeill S Koti M van Wijnen AJ Squire JA Zielenska M. Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma. PLoS One (2014) 9(5):e95843.10.1371/journal.pone.009584324835790
52. Albihn A Johnsen JI Henriksson MA. MYC in oncogenesis and as a target for cancer therapies. Adv Cancer Res (2010) 107:163–224.10.1016/S0065-230X(10)07006-520399964
53. Pompetti F Rizzo P Simon RM Freidlin B Mew DJ Pass HI et al. Oncogene alterations in primary, recurrent, and metastatic human bone tumors. J Cell Biochem (1996) 63(1):37–50.10.1002/(SICI)1097-4644(199610)63:1<37::AID-JCB3>3.0.CO;2-08891902
54. Gamberi G Benassi MS Bohling T Ragazzini P Molendini L Sollazzo MR et al. C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology (1998) 55(6):556–63.10.1159/0000119129778623
55. Thornton JE Gregory RI. How does Lin28 let-7 control development and disease? Trends Cell Biol (2012) 22(9):474–82.10.1016/j.tcb.2012.06.00122784697
56. Thayanithy V Sarver AL Kartha RV Li L Angstadt AY Breen M et al. Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone (2012) 50(1):171–81.10.1016/j.bone.2011.10.01222037351
57. Liu Z Zhang G Li J Liu J Lv P. The tumor-suppressive microRNA-135b targets c-myc in osteoscarcoma. PLoS One (2014) 9(7):e102621.10.1371/journal.pone.010262125025684
58. Xu N Li Z Yu Z Yan F Liu Y Lu X et al. MicroRNA-33b suppresses migration and invasion by targeting c-Myc in osteosarcoma cells. PLoS One (2014) 9(12):e115300.10.1371/journal.pone.011530025546234
59. Liu JM Long XH Zhang GM Zhou Y Chen XY Huang SH et al. Let-7g reverses malignant phenotype of osteosarcoma cells by targeting aurora-B. Int J Clin Exp Pathol (2014) 7(8):4596–606.25197332
60. Di Fiore R Fanale D Drago-Ferrante R Chiaradonna F Giuliano M De Blasio A et al. Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness. J Cell Physiol (2013) 228(6):1189–201.10.1002/jcp.2427223129384
61. Wang X Cao L Wang Y Wang X Liu N You Y. Regulation of let-7 and its target oncogenes (review). Oncol Lett (2012) 3(5):955–60.10.3892/ol.2012.60922783372
62. Pratap J Lian JB Javed A Barnes GL van Wijnen AJ Stein JL et al. Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev (2006) 25(4):589–600.10.1007/s10555-006-9032-017165130
63. Nathan SS Pereira BP Zhou YF Gupta A Dombrowski C Soong R et al. Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma. Mol Biol Rep (2009) 36(1):153–8.10.1007/s11033-008-9378-118931939
64. Sadikovic B Thorner P Chilton-Macneill S Martin JW Cervigne NK Squire J et al. Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy. BMC Cancer (2010) 10:202.10.1186/1471-2407-10-20220465837
65. He Y Meng C Shao Z Wang H Yang S. MiR-23a functions as a tumor suppressor in osteosarcoma. Cell Physiol Biochem (2014) 34(5):1485–96.10.1159/00036635325322765
66. Zuo B Zhu J Li J Wang C Zhao X Cai G et al. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting Runx2. J Bone Miner Res (2015) 30(2):330–45.10.1002/jbmr.235225195535
67. Taipaleenmäki H Browne G Akech J Zustin J van Wijnen AJ Stein JL et al. Targeting of Runx2 by miR-135 and miR-203 impairs progression of breast cancer and metastatic bone disease. Cancer Res (2015) 75(7):1433–44.10.1158/0008-5472.CAN-14-102625634212
68. Hu N Feng C Jiang Y Miao Q Liu H. Regulative effect of Mir-205 on osteogenic differentiation of bone mesenchymal stem cells (BMSCs): possible role of SATB2/Runx2 and ERK/MAPK pathway. Int J Mol Sci (2015) 16(5):10491–506.10.3390/ijms16051049125961955
69. Sampson VB Gorlick R Kamara D Anders Kolb E. A review of targeted therapies evaluated by the pediatric preclinical testing program for osteosarcoma. Front Oncol (2013) 3:132.10.3389/fonc.2013.0013223755370
70. Kolb EA Gorlick R. Development of IGF-IR inhibitors in pediatric sarcomas. Curr Oncol Rep (2009) 11(4):307–13.10.1007/s11912-009-0043-119508836
71. Durfort T Tkach M Meschaninova MI Rivas MA Elizalde PV Venyaminova AG et al. Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model. PLoS One (2012) 7(1):e29213.10.1371/journal.pone.002921322235273
72. Burrow S Andrulis IL Pollak M Bell RS. Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma. J Surg Oncol (1998) 69(1):21–7.10.1002/(SICI)1096-9098(199809)69:1<21::AID-JSO5>3.0.CO;2-M9762887
73. Sasaki K Hitora T Nakamura O Kono R Yamamoto T. The role of MAPK pathway in bone and soft tissue tumors. Anticancer Res (2011) 31(2):549–53.21378337
74. Chandhanayingyong C Kim Y Staples JR Hahn C Lee FY. MAPK/ERK signaling in osteosarcomas, Ewing sarcomas and chondrosarcomas: therapeutic implications and future directions. Sarcoma (2012) 2012:404810.10.1155/2012/40481022577336
75. Han K Zhao T Chen X Bian N Yang T Ma Q et al. microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R. Int J Oncol (2014) 45(4):1437–49.10.3892/ijo.2014.257125096247
76. Song Y Zhao F Wang Z Liu Z Chiang Y Xu Y et al. Inverse association between miR-194 expression and tumor invasion in gastric cancer. Ann Surg Oncol (2012) 19(Suppl 3):S509–17.10.1245/s10434-011-1999-221845495
77. Wu X Liu T Fang O Leach LJ Hu X Luo Z. miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1). Oncogene (2014) 33(12):1506–14.10.1038/onc.2013.10823584484
78. Zhao H Li M Li L Yang X Lan G Zhang Y. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS One (2013) 8(12):e83571.10.1371/journal.pone.008357124391788
79. Naka T Iwamoto Y Shinohara N Ushijima M Chuman H Tsuneyoshi M. Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone tumors. Mod Pathol (1997) 10(8):832–8.9267827
80. Ebos JM Lee CR Kerbel RS. Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy. Clin Cancer Res (2009) 15(16):5020–5.10.1158/1078-0432.CCR-09-009519671869
81. Engelman JA Zejnullahu K Mitsudomi T Song Y Hyland C Park JO et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science (2007) 316(5827):1039–43.10.1126/science.114147817463250
82. Yan K Gao J Yang T Ma Q Qiu X Fan Q et al. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One (2012) 7(3):e33778.10.1371/journal.pone.003377822457788
83. Duan Z Choy E Harmon D Liu X Susa M Mankin H et al. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther (2011) 10(8):1337–45.10.1158/1535-7163.MCT-11-009621666078
84. Rong S Donehower LA Hansen MF Strong L Tainsky M Jeffers M et al. Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients. Cancer Res (1995) 55(9):1963–70.7728766
85. Zhang L Lyer AK Yang X Kobayashi E Guo Y Mankin H et al. Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells. Int J Nanomedicine (2015) 10:2913–24.10.2147/IJN.S7914325931818
86. Yu Y Luk F Yang JL Walsh WR. Ras/Raf/MEK/ERK pathway is associated with lung metastasis of osteosarcoma in an orthotopic mouse model. Anticancer Res (2011) 31(4):1147–52.21508358
87. Xi Y Chen Y. Oncogenic and therapeutic targeting of PTEN loss in bone malignancies. J Cell Biochem (2015) 116(9):1837–47.10.1002/jcb.2515925773992
88. Freeman SS Allen SW Ganti R Wu J Ma J Su X et al. Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors. Cancer (2008) 113(6):1453–61.10.1002/cncr.2378218704985
89. Zhao G Cai C Yang T Qiu X Liao B Li W et al. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One (2013) 8(1):e53906.10.1371/journal.pone.005390623372675
90. Gao Y Luo LH Li S Yang C. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun (2014) 444(2):230–4.10.1016/j.bbrc.2014.01.06124462867
91. Lin S Shao NN Fan L Ma XC Pu FF Shao ZW. Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR. J Huazhong Univ Sci Technolog Med Sci (2014) 34(6):889–95.10.1007/s11596-014-1369-y25480586
92. Xu Y An Y Wang Y Zhang C Zhang H Huang C et al. miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncol Rep (2013) 29(5):2019–24.10.3892/or.2013.233823483142
93. Na KY Kim YW Park YK. Mitogen-activated protein kinase pathway in osteosarcoma. Pathology (2012) 44(6):540–6.10.1097/PAT.0b013e32835803bc22935974
94. Zhang X Guo Q Chen J Chen Z. Quercetin enhances cisplatin sensitivity of human osteosarcoma cells by modulating microRNA-217-KRAS axis. Mol Cells (2015) 38(7):638–42.10.14348/molcells.2015.003726062553
95. Wang Q Cai J Wang J Xiong C Zhao J. MiR-143 inhibits EGFR-signaling-dependent osteosarcoma invasion. Tumour Biol (2014) 35(12):12743–8.10.1007/s13277-014-2600-y25227664
96. Gialeli C Theocharis AD Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J (2011) 278(1):16–27.10.1111/j.1742-4658.2010.07919.x21087457
97. Fulda S Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene (2006) 25(34):4798–811.10.1038/sj.onc.120960816892092
98. Ji F Zhang H Wang Y Li M Xu W Kang Y et al. MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone (2013) 56(1):220–6.10.1016/j.bone.2013.05.02023756231
99. Dong Y Zhao J Wu CW Zhang L Liu X Kang W et al. Tumor suppressor functions of miR-133a in colorectal cancer. Mol Cancer Res (2013) 11(9):1051–60.10.1158/1541-7786.MCR-13-006123723074
100. Pignochino Y Grignani G Cavalloni G Motta M Tapparo M Bruno S et al. Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer (2009) 8:118.10.1186/1476-4598-8-11820003259
101. Volinia S Galasso M Costinean S Tagliavini L Gamberoni G Drusco A et al. Reprogramming of miRNA networks in cancer and leukemia. Genome Res (2010) 20(5):589–99.10.1101/gr.098046.10920439436
102. Huang G Nishimoto K Zhou Z Hughes D Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res (2012) 72(4):908–16.10.1158/0008-5472.CAN-11-146022186140
103. Arabi L Gsponer JR Smida J Nathrath M Perrina V Jundt G et al. Upregulation of the miR-17-92 cluster and its two paralog in osteosarcoma – reasons and consequences. Genes Cancer (2014) 5(1–2):56–63.24955218
104. Meyers PA Heller G Healey JH Huvos A Applewhite A Sun M et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol (1993) 11(3):449–53.8445419
105. Krishnan K Khanna C Helman LJ. The biology of metastases in pediatric sarcomas. Cancer J (2005) 11(4):306–13.10.1097/00130404-200507000-0000616197720
106. Rath N Olson MF. Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy. EMBO Rep (2012) 13(10):900–8.10.1038/embor.2012.12722964758
107. Zhou X Wei M Wang W. MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun (2013) 437(4):653–8.10.1016/j.bbrc.2013.07.03323872151
108. Wang Y Zhao W Fu Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem (2013) 384(1–2):105–11.10.1007/s11010-013-1786-423975506
109. Lei P Xie J Wang L Yang X Dai Z Hu Y. microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1. Mol Med Rep (2014) 10(1):155–60.10.3892/mmr.2014.219524789502
110. Wang W Zhou X Wei M. MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2. Oncotarget (2015) 6(12):10297–308.25912304
111. Zhang B Cao X Liu Y Cao W Zhang F Zhang S et al. Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer. BMC Cancer (2008) 8:83.10.1186/1471-2407-8-8318373849
112. Yamada T Oshima T Yoshihara K Tamura S Kanazawa A Inagaki D et al. Overexpression of MMP-13 gene in colorectal cancer with liver metastasis. Anticancer Res (2010) 30(7):2693–9.20683000
113. Xiang X Mei H Zhao X Pu J Li D Qu H et al. miRNA-337-3p suppresses neuroblastoma progression by repressing the transcription of matrix metalloproteinase 14. Oncotarget (2015).26084291
114. Jia LF Wei SB Mitchelson K Gao Y Zheng YF Meng Z et al. miR-34a inhibits migration and invasion of tongue squamous cell carcinoma via targeting MMP9 and MMP14. PLoS One (2014) 9(9):e108435.10.1371/journal.pone.010843525268950
115. Caubet JF Bernaudin JF. Expression of the c-fos proto-oncogene in bone, cartilage and tooth forming tissues during mouse development. Biol Cell (1988) 64(1):101–4.10.1016/0248-4900(88)90100-13147115
116. Schmidt J Livne E Erfle V Gossner W Silbermann M. Morphology and in vivo growth characteristics of an atypical murine proliferative osseous lesion induced in vitro. Cancer Res (1986) 46(6):3090–8.3009010
117. Wu JX Carpenter PM Gresens C Keh R Niman H Morris JW et al. The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene (1990) 5(7):989–1000.2115647
118. Wang ZQ Liang J Schellander K Wagner EF Grigoriadis AE. c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. Cancer Res (1995) 55(24):6244–51.8521421
119. Tao T Wang Y Luo H Yao L Wang L Wang J et al. Involvement of FOS-mediated miR-181b/miR-21 signalling in the progression of malignant gliomas. Eur J Cancer (2013) 49(14):3055–63.10.1016/j.ejca.2013.05.01023810250
120. Hornicek FJ Gebhardt MC Wolfe MW Kharrazi FD Takeshita H Parekh SG et al. P-glycoprotein levels predict poor outcome in patients with osteosarcoma. Clin Orthop Relat Res (2000) (373):11–7.10.1097/00003086-200004000-0000310810457
121. Zhu H Wu H Liu X Evans BR Medina DJ Liu CG et al. Role of microRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol (2008) 76(5):582–8.10.1016/j.bcp.2008.06.00718619946
122. Salah Z Arafeh R Maximov V Galasso M Khawaled S Abou-Sharieha S et al. miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget (2015) 6(7):4920–35.25749032
123. Wu X Bhayani MK Dodge CT Nicoloso MS Chen Y Yan X et al. Coordinated targeting of the EGFR signaling axis by microRNA-27a*. Oncotarget (2013) 4(9):1388–98.23963114
124. Chen L Wang Q Wang GD Wang HS Huang Y Liu XM et al. miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett (2013) 587(9):1366–72.10.1016/j.febslet.2013.03.00723507142
125. Diederichs S Haber DA. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res (2006) 66(12):6097–104.10.1158/0008-5472.CAN-06-053716778182
126. Wu M Jolicoeur N Li Z Zhang L Fortin Y L’Abbe D et al. Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis (2008) 29(9):1710–6.10.1093/carcin/bgn07318356149
127. Garcia DM Baek D Shin C Bell GW Grimson A Bartel DP. Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs. Nat Struct Mol Biol (2011) 18(10):1139–46.10.1038/nsmb.211521909094
128. Betel D Wilson M Gabow A Marks DS Sander C. The microRNA.org resource: targets and expression. Nucleic Acids Res (2008) 36(Database issue):D149–53.10.1093/nar/gkm99518158296
129. Selbach M Schwanhausser B Thierfelder N Fang Z Khanin R Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature (2008) 455(7209):58–63.10.1038/nature0722818668040
130. Lewis BP Shih IH Jones-Rhoades MW Bartel DP Burge CB. Prediction of mammalian microRNA targets. Cell (2003) 115(7):787–98.10.1016/S0092-8674(03)01018-314697198
131. Broderick JA Zamore PD. MicroRNA therapeutics. Gene Ther (2011) 18(12):1104–10.10.1038/gt.2011.5021525952