Top

Published in:

01-01-2019 | Original Article

Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma

Authors: L. E. A. Delsin, G. M. Roberto, P. F. Fedatto, E. E. Engel, C. A. Scrideli, L. G. Tone, M. S. Brassesco

Published in: Pathology & Oncology Research | Issue 1/2019

Abstract

miRNAs have been identified as key regulators of almost all cellular processes, therefore, their dysregulation is involved with several diseases, including cancer. miRNAs specifically related to the metastastic cascade are called metastamiRs and can be involved with different steps of this process, including loss of adhesion. Osteosarcoma (OS) is the most common primary malignant pediatric bone tumor that often presents metastatic disease at diagnosis; therefore, a deeper study of adhesion-associated miRNAs could shed light on its pathophysiology. Online databases were used to select four miRNAs (miR-139; miR-181b; miR-584; miR-708) predicted or validated to target proteins related to adherent junctions and focal adhesion pathways, and their expression levels and possible associations with clinical features evaluated in primary OS samples. Our results showed downregulation of miR-139-5p and miR-708-5p in OS samples compared to non-neoplastic controls. Moreover, lower expression of miR-708-5p was associated with poor overall survival and higher expression of miR-181b-5p related to worst chemotherapy response (low HUVOS level). Based on these results, we selected miR-139-5p and miR-708-5p for further functional testing. Inducing the expression of miR-139-5p diminished the clonogenic capacity of the HOS cell line, while upregulation of miR-708-5p was related to a lower cellular adhesion. In summary, this work identified new signatures of microRNA dysregulation that may serve as useful prognostic markers in this aggressive pediatric bone tumor.

Gee HE, Ivan C, Calin GA, Ivan M (2014) HypoxamiRs and cancer: from biology to targeted therapy. Antioxid Redox Signal 21(8):1220–1238. https://doi.org/10.1089/ars.2013.5639 CrossRefPubMedPubMedCentral

Olivieri F, Rippo MR, Procopio AD, Fazioli F (2013) Circulating inflamma-miRs in aging and age-related diseases. Front Genet 4:121. https://doi.org/10.3389/fgene.2013.00121 CrossRefPubMedPubMedCentral

Schickel R, Boyerinas B, Park SM, Peter ME (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27(45):5959–5974. https://doi.org/10.1038/onc.2008.274 CrossRefPubMed

Tutar L, Tutar E, Özgür A, Tutar Y (2015) Therapeutic Targeting of microRNAs in Cancer: Future Perspectives. Drug Dev Res 76(7):382–388. https://doi.org/10.1002/ddr.21273 CrossRefPubMed

Hurst DR, Edmonds MD, Welch DR (2009) Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res 69(19):7495–7498. https://doi.org/10.1158/0008-5472.CAN-09-2111 CrossRefPubMedPubMedCentral

Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P (2008) MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A 105(15):5874–5878. https://doi.org/10.1073/pnas.0801130105 CrossRefPubMedPubMedCentral

Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175):147–152. https://doi.org/10.1038/nature06487 CrossRefPubMedPubMedCentral

Gregory PA, Bracken CP, Bert AG, Goodall GJ (2008) MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle 7(20):3112–3118. https://doi.org/10.4161/cc.7.20.6851 CrossRefPubMed

Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449(7163):682–688. https://doi.org/10.1038/nature06174 CrossRefPubMed

10.

Wang Y, Li Z, Zhao X, Zuo X, Peng Z (2016) miR-10b promotes invasion by targeting HOXD10 in colorectal cancer. Oncol Lett 12(1):488–494. https://doi.org/10.3892/ol.2016.4628 CrossRefPubMedPubMedCentral

11.

Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY (2008) MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18(3):350–359. https://doi.org/10.1038/cr.2008.24 CrossRefPubMed

12.

Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR (2009) Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 69(4):1279–1283. https://doi.org/10.1158/0008-5472.CAN-08-3559 CrossRefPubMedPubMedCentral

13.

Massagué J, Obenauf AC (2016) Metastatic colonization by circulating tumour cells. Nature 529(7586):298–306. https://doi.org/10.1038/nature17038 CrossRefPubMedPubMedCentral

14.

Talmadge JE, Fidler IJ (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 70(14):5649–5669. https://doi.org/10.1158/0008-5472.CAN-10-1040 CrossRefPubMedPubMedCentral

15.

Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA (2009) MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer 9(4):293–302. https://doi.org/10.1038/nrc2619 CrossRefPubMed

16.

Le XF, Merchant O, Bast RC, Calin GA (2010) The Roles of MicroRNAs in the Cancer Invasion-Metastasis Cascade. Cancer Microenviron 3(1):137–147. https://doi.org/10.1007/s12307-010-0037-4 CrossRefPubMedPubMedCentral

17.

le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafrè SA, Farace MG, Agami R (2007) Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26(15):3699–3708. https://doi.org/10.1038/sj.emboj.7601790 CrossRefPubMedPubMedCentral

18.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E (2007) let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131(6):1109–1123. https://doi.org/10.1016/j.cell.2007.10.054 CrossRefPubMed

19.

Gorlick R, Khanna C (2010) Osteosarcoma. J Bone Miner Res 25(4):683–691. https://doi.org/10.1002/jbmr.77 CrossRefPubMed

20.

Kushlinskii NE, Fridman MV, Braga EA (2016) Molecular Mechanisms and microRNAs in Osteosarcoma Pathogenesis. Biochemistry (Mosc) 81(4):315–328. https://doi.org/10.1134/S0006297916040027 CrossRef

21.

Ram Kumar RM, Boro A, Fuchs B (2016) Involvement and Clinical Aspects of MicroRNA in Osteosarcoma. Int J Mol Sci 17(6). https://doi.org/10.3390/ijms17060877

22.

Geng S, Zhang X, Chen J, Liu X, Zhang H, Xu X, Ma Y, Li B, Zhang Y, Bi Z, Yang C (2014) The tumor suppressor role of miR-124 in osteosarcoma. PLoS One 9(6):e91566. https://doi.org/10.1371/journal.pone.0091566 CrossRefPubMedPubMedCentral

23.

Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y (2013) MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS One 8(12):e83571. https://doi.org/10.1371/journal.pone.0083571 CrossRefPubMedPubMedCentral

24.

Huang J, Gao K, Lin J, Wang Q (2014) MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61. Tumour Biol 35(2):1095–1100. https://doi.org/10.1007/s13277-013-1146-8 CrossRefPubMed

25.

Wu P, Liang J, Yu F, Zhou Z, Tang J, Li K (2016) miR-145 promotes osteosarcoma growth by reducing expression of the transcription factor friend leukemia virus integration 1. Oncotarget. doi:10.18632/oncotarget.9948

26.

Li X, Yang H, Tian Q, Liu Y, Weng Y (2014) Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma. Neoplasma 61(4):453–460. https://doi.org/10.4149/neo_2014_056 CrossRefPubMed

27.

Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES (2012) miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res 72(4):908–916. https://doi.org/10.1158/0008-5472.CAN-11-1460 CrossRefPubMed

28.

Ma C, Zhan C, Yuan H, Cui Y, Zhang Z (2016) MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma. Oncol Rep 35(6):3257–3264. https://doi.org/10.3892/or.2016.4718 CrossRefPubMed

29.

Xu SH, Yang YL, Han SM, Wu ZH (2014) MicroRNA-9 expression is a prognostic biomarker in patients with osteosarcoma. World J Surg Oncol 12:195. https://doi.org/10.1186/1477-7819-12-195 CrossRefPubMedPubMedCentral

30.

Maire G, Martin JW, Yoshimoto M, Chilton-MacNeill S, Zielenska M, Squire JA (2011) Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet 204(3):138–146. https://doi.org/10.1016/j.cancergen.2010.12.012 CrossRefPubMed

31.

Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, Lovat F, LeBlanc K, Palatini J, Randall RL, Volinia S, Stein GS, Croce CM, Lian JB, Aqeilan RI (2012) miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res 72(7):1865–1877. https://doi.org/10.1158/0008-5472.CAN-11-2663 CrossRefPubMedPubMedCentral

32.

Namløs HM, Meza-Zepeda LA, Barøy T, Østensen IH, Kresse SH, Kuijjer ML, Serra M, Bürger H, Cleton-Jansen AM, Myklebost O (2012) Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One 7(10):e48086. https://doi.org/10.1371/journal.pone.0048086 CrossRefPubMedPubMedCentral

33.

Lulla RR, Costa FF, Bischof JM, Chou PM, de F Bonaldo M, Vanin EF, Soares MB (2011) Identification of Differentially Expressed MicroRNAs in Osteosarcoma. Sarcoma 2011:732690. https://doi.org/10.1155/2011/732690 CrossRefPubMedPubMedCentral

34.

Wang W, Zhou X, Wei M (2015) MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2. Oncotarget 6(12):10297–10308. 10.18632/oncotarget.3305 CrossRefPubMedPubMedCentral

35.

Shen L, Wang P, Yang J, Li X (2014) MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS One 9(10):e109138. https://doi.org/10.1371/journal.pone.0109138 CrossRefPubMedPubMedCentral

36.

Han K, Chen X, Bian N, Ma B, Yang T, Cai C, Fan Q, Zhou Y, Zhao TB (2015) MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1. Oncotarget 6 (11):8875-8889. doi:10.18632/oncotarget.3560

37.

Poos K, Smida J, Nathrath M, Maugg D, Baumhoer D, Korsching E (2013) How microRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation. PLoS Comput Biol 9(8):e1003210. https://doi.org/10.1371/journal.pcbi.1003210 CrossRefPubMedPubMedCentral

38.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262 CrossRefPubMed

39.

Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C (2006) Clonogenic assay of cells in vitro. Nat Protoc 1(5):2315–2319. https://doi.org/10.1038/nprot.2006.339 CrossRefPubMed

40.

Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671–675CrossRef

41.

Zhang J, Yan YG, Wang C, Zhang SJ, Yu XH, Wang WJ (2015) MicroRNAs in osteosarcoma. Clin Chim Acta 444:9–17. https://doi.org/10.1016/j.cca.2015.01.025 CrossRefPubMed

42.

Zhang HD, Jiang LH, Sun DW, Li J, Tang JH (2015) MiR-139-5p: promising biomarker for cancer. Tumour Biol 36(3):1355–1365. https://doi.org/10.1007/s13277-015-3199-3 CrossRefPubMed

43.

Chen X, Shi K, Wang Y, Song M, Zhou W, Tu H, Lin Z (2015) Clinical value of integrated-signature miRNAs in colorectal cancer: miRNA expression profiling analysis and experimental validation. Oncotarget 6 (35):37544-37556. doi:10.18632/oncotarget.6065

44.

Liu X, Duan B, Dong Y, He C, Zhou H, Sheng H, Gao H, Zhang X (2014) MicroRNA-139-3p indicates a poor prognosis of colon cancer. Int J Clin Exp Pathol 7(11):8046–8052PubMedPubMedCentral

45.

Yonemori M, Seki N, Yoshino H, Matsushita R, Miyamoto K, Nakagawa M, Enokida H (2016) Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer. Cancer Sci 107(9):1233–1242. https://doi.org/10.1111/cas.13002 CrossRefPubMedPubMedCentral

46.

Ratert N, Meyer HA, Jung M, Lioudmer P, Mollenkopf HJ, Wagner I, Miller K, Kilic E, Erbersdobler A, Weikert S, Jung K (2013) miRNA profiling identifies candidate mirnas for bladder cancer diagnosis and clinical outcome. J Mol Diagn 15(5):695–705. https://doi.org/10.1016/j.jmoldx.2013.05.008 CrossRefPubMed

47.

Wang Z, Ding Q, Li Y, Liu Q, Wu W, Wu L, Yu H (2016) Reanalysis of microRNA expression profiles identifies novel biomarkers for hepatocellular carcinoma prognosis. Tumour Biol. https://doi.org/10.1007/s13277-016-5369-3

48.

Haakensen VD, Nygaard V, Greger L, Aure MR, Fromm B, Bukholm IR, Lüders T, Chin SF, Git A, Caldas C, Kristensen VN, Brazma A, Børresen-Dale AL, Hovig E, Helland Å (2016) Subtype-specific micro-RNA expression signatures in breast cancer progression. Int J Cancer 139(5):1117–1128. https://doi.org/10.1002/ijc.30142 CrossRefPubMed

49.

Rask L, Balslev E, Søkilde R, Høgdall E, Flyger H, Eriksen J, Litman T (2014) Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status. Cell Oncol (Dordr) 37(3):215–227. https://doi.org/10.1007/s13402-014-0176-6 CrossRef

50.

Krishnan K, Steptoe AL, Martin HC, Pattabiraman DR, Nones K, Waddell N, Mariasegaram M, Simpson PT, Lakhani SR, Vlassov A, Grimmond SM, Cloonan N (2013) miR-139-5p is a regulator of metastatic pathways in breast cancer. RNA 19(12):1767–1780. https://doi.org/10.1261/rna.042143.113 CrossRefPubMedPubMedCentral

51.

Qiu G, Lin Y, Zhang H, Wu D (2015) miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2. Biochem Biophys Res Commun 463(3):315–321. https://doi.org/10.1016/j.bbrc.2015.05.062 CrossRefPubMed

52.

Yue S, Wang L, Zhang H, Min Y, Lou Y, Sun H, Jiang Y, Zhang W, Liang A, Guo Y, Chen P, Lv G, Zong Q, Li Y (2015) miR-139-5p suppresses cancer cell migration and invasion through targeting ZEB1 and ZEB2 in GBM. Tumour Biol 36(9):6741–6749. https://doi.org/10.1007/s13277-015-3372-8 CrossRefPubMed

53.

Li Q, Liang X, Wang Y, Meng X, Xu Y, Cai S, Wang Z, Liu J, Cai G (2016) miR-139-5p Inhibits the Epithelial-Mesenchymal Transition and Enhances the Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating BCL2. Sci Rep 6:27157. doi:https://doi.org/10.1038/srep27157

54.

Watanabe K, Amano Y, Ishikawa R, Sunohara M, Kage H, Ichinose J, Sano A, Nakajima J, Fukayama M, Yatomi Y, Nagase T, Ohishi N, Takai D (2015) Histone methylation-mediated silencing of miR-139 enhances invasion of non-small-cell lung cancer. Cancer Med 4(10):1573–1582. https://doi.org/10.1002/cam4.505 CrossRefPubMedPubMedCentral

55.

Liu Y, Uzair-Ur-Rehman GY, Liang H, Cheng R, Yang F, Hong Y, Zhao C, Liu M, Yu M, Zhou X, Yin K, Chen J, Zhang J, Zhang CY, Zhi F, Chen X (2016) miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4. Protein Cell 7(10):722–734. https://doi.org/10.1007/s13238-016-0313-2 CrossRefPubMedPubMedCentral

56.

Huang S, Wang J, Li J, Luo Q, Zhao M, Zheng L, Dong X, Chen C, Che Y, Liu P, Qi J, Huang C (2016) Serum microRNA expression profile as a diagnostic panel for gastric cancer. Jpn J Clin Oncol 46(9):811–818. https://doi.org/10.1093/jjco/hyw085 CrossRefPubMed

57.

Zheng Y, Lv X, Wang X, Wang B, Shao X, Huang Y, Shi L, Chen Z, Huang J, Huang P (2016) MiR-181b promotes chemoresistance in breast cancer by regulating Bim expression. Oncol Rep 35(2):683–690. https://doi.org/10.3892/or.2015.4417 CrossRefPubMed

58.

Sochor M, Basova P, Pesta M, Dusilkova N, Bartos J, Burda P, Pospisil V, Stopka T (2014) Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer 14:448. https://doi.org/10.1186/1471-2407-14-448 CrossRefPubMedPubMedCentral

59.

Liu J, Shi W, Wu C, Ju J, Jiang J (2014) miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review). Biomed Rep 2(1):7–11. https://doi.org/10.3892/br.2013.199 CrossRefPubMed

60.

Cai B, An Y, Lv N, Chen J, Tu M, Sun J, Wu P, Wei J, Jiang K, Miao Y (2013) miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2. Oncol Rep 29(5):1769–1776. https://doi.org/10.3892/or.2013.2297 CrossRefPubMed

61.

Wang J, Sai K, Chen FR, Chen ZP (2013) miR-181b modulates glioma cell sensitivity to temozolomide by targeting MEK1. Cancer Chemother Pharmacol 72(1):147–158. https://doi.org/10.1007/s00280-013-2180-3 CrossRefPubMed

62.

Wang X, Chen X, Meng Q, Jing H, Lu H, Yang Y, Cai L, Zhao Y (2015) MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC. Sci Rep 5:17618. https://doi.org/10.1038/srep17618 CrossRefPubMedPubMedCentral

63.

Shao JL, Li ZZ, Wang L, Jiao GL, Zhou ZG, Sun GD (2016) microRNA-181b promotes migration and invasion of osteosarcoma cells by targeting N-myc downstream regulated gene 2. Nan Fang Yi Ke Da Xue Xue Bao 36(3):321–326PubMed

64.

Nakajima G, Hayashi K, Xi Y, Kudo K, Uchida K, Takasaki K, Yamamoto M, Ju J (2006) Non-coding MicroRNAs hsa-let-7g and hsa-miR-181b are Associated with Chemoresponse to S-1 in Colon Cancer. Cancer Genomics Proteomics 3(5):317–324PubMedPubMedCentral

65.

Hu L, Ai J, Long H, Liu W, Wang X, Zuo Y, Li Y, Wu Q, Deng Y (2016) Integrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer. Oncotarget 7 (8):8441-8454. doi:10.18632/oncotarget.7264

66.

Li X, Li D, Zhuang Y, Shi Q, Wei W, Ju X (2013) Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL. Pediatr Blood Cancer 60(12):2060–2067. https://doi.org/10.1002/pbc.24583 CrossRefPubMed

67.

Li G, Yang F, Xu H, Yue Z, Fang X, Liu J (2015) MicroRNA-708 is downregulated in hepatocellular carcinoma and suppresses tumor invasion and migration. Biomed Pharmacother 73:154–159. https://doi.org/10.1016/j.biopha.2015.05.010 CrossRefPubMed

68.

Lei SL, Zhao H, Yao HL, Chen Y, Lei ZD, Liu KJ, Yang Q (2014) Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells. Oncol Lett 8(4):1768–1774. https://doi.org/10.3892/ol.2014.2328 CrossRefPubMedPubMedCentral

69.

Lin KT, Yeh YM, Chuang CM, Yang SY, Chang JW, Sun SP, Wang YS, Chao KC, Wang LH (2015) Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B. Nat Commun 6:5917. https://doi.org/10.1038/ncomms6917 CrossRefPubMedPubMedCentral

70.

Ryu S, McDonnell K, Choi H, Gao D, Hahn M, Joshi N, Park SM, Catena R, Do Y, Brazin J, Vahdat LT, Silver RB, Mittal V (2013) Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Cancer Cell 23(1):63–76. https://doi.org/10.1016/j.ccr.2012.11.019 CrossRefPubMed

71.

Saini S, Yamamura S, Majid S, Shahryari V, Hirata H, Tanaka Y, Dahiya R (2011) MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells. Cancer Res 71(19):6208–6219. https://doi.org/10.1158/0008-5472.CAN-11-0073 CrossRefPubMedPubMedCentral

72.

Yan W, Li R, Liu Y, Yang P, Wang Z, Zhang C, Bao Z, Zhang W, You Y, Jiang T (2014) MicroRNA expression patterns in the malignant progression of gliomas and a 5-microRNA signature for prognosis. Oncotarget 5(24):12908–12915. 10.18632/oncotarget.2679 CrossRefPubMedPubMedCentral

73.

Xue H, Guo X, Han X, Yan S, Zhang J, Xu S, Li T, Zhang P, Gao X, Liu Q, Li G (2016) MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1. Oncotarget 7(4):4785–4805. 10.18632/oncotarget.6735 CrossRefPubMed

74.

Wang XP, Deng XL, Li LY (2014) MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma. Int J Clin Exp Pathol 7(12):8573–8582PubMedPubMedCentral

75.

Guled M, Lahti L, Lindholm PM, Salmenkivi K, Bagwan I, Nicholson AG, Knuutila S (2009) CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis. Genes Chromosomes Cancer 48(7):615–623. https://doi.org/10.1002/gcc.20669 CrossRefPubMed

76.

Gaedcke J, Grade M, Camps J, Søkilde R, Kaczkowski B, Schetter AJ, Difilippantonio MJ, Harris CC, Ghadimi BM, Møller S, Beissbarth T, Ried T, Litman T (2012) The rectal cancer microRNAome--microRNA expression in rectal cancer and matched normal mucosa. Clin Cancer Res 18(18):4919–4930. https://doi.org/10.1158/1078-0432.CCR-12-0016 CrossRefPubMedPubMedCentral

77.

Ueno K, Hirata H, Shahryari V, Chen Y, Zaman MS, Singh K, Tabatabai ZL, Hinoda Y, Dahiya R (2011) Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer 104(2):308–315. https://doi.org/10.1038/sj.bjc.6606028 CrossRefPubMed

78.

Xiang J, Wu Y, Li DS, Wang ZY, Shen Q, Sun TQ, Guan Q, Wang YJ (2015) miR-584 Suppresses Invasion and Cell Migration of Thyroid Carcinoma by Regulating the Target Oncogene ROCK1. Oncol Res Treat 38(9):436–440. https://doi.org/10.1159/000438967 CrossRefPubMed

Title: Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma
Authors: L. E. A. Delsin
G. M. Roberto
P. F. Fedatto
E. E. Engel
C. A. Scrideli
L. G. Tone
M. S. Brassesco
Publication date: 01-01-2019
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 1/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-017-0316-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

NRG-1 Stimulates Serum DJ-1 Increase in Breast Cancers

RETRACTED ARTICLE: Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 through the Wnt Signaling Pathway

In Vitro Study of the Effects of Denosumab on Giant Cell Tumor of Bone: Comparison with Zoledronic Acid

Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional Cell Carcinoma of Bladder

Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy

Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer