{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:04:41Z","timestamp":1776744281791,"version":"3.51.2"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D08CA-053(DLD)"],"award-info":[{"award-number":["D08CA-053(DLD)"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D13CA-058 (DLD)"],"award-info":[{"award-number":["D13CA-058 (DLD)"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["9T32OD010437-11"],"award-info":[{"award-number":["9T32OD010437-11"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>MicroRNAs (miRNA) are small non-coding RNA molecules involved in post-transcriptional gene regulation. Deregulation of miRNA expression occurs in cancer, and miRNA expression profiles have been associated with diagnosis and prognosis in many cancers. Osteosarcoma (OS), an aggressive primary tumor of bone, affects ~10,000 dogs each year. Though survival has improved with the addition of chemotherapy, up to 80% of canine patients will succumb to metastatic disease. Reliable prognostic markers are lacking for this disease. miRNAs are attractive targets of biomarker discovery efforts due to their increased stability in easily obtained body fluids as well as within fixed tissue. Previous studies in our laboratory demonstrated that dysregulation of genes in aggressive canine OS tumors that participate in miRNA regulatory networks is reportedly disrupted in OS or other cancers. We utilized RT-qPCR in a 384-well-plate system to measure the relative expression of 190 miRNAs in 14 canine tumors from two cohorts of dogs with good or poor outcome (disease-free interval &amp;gt;300 or &amp;lt;100 days, respectively). Differential expression analysis in this subset guided the selection of candidate miRNAs in tumors and serum samples from larger groups of dogs. We ultimately identified a tumor-based three-miR Cox proportional hazards regression model and a serum-based two-miR model, each being able to distinguish patients with good and poor prognosis via Kaplan\u2013Meier analysis with log rank test. Additionally, we integrated miRNA and gene expression data to identify potentially important miRNA\u2013mRNA interactions that are disrupted in canine OS. Integrated analyses of miRNAs in the three-miR predictive model and disrupted genes from previous expression studies suggest the contribution of the primary tumor microenvironment to the metastatic phenotype of aggressive tumors.<\/jats:p>","DOI":"10.3389\/fvets.2021.637622","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T06:59:10Z","timestamp":1618469950000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["MicroRNA Expression Changes and Integrated Pathways Associated With Poor Outcome in Canine Osteosarcoma"],"prefix":"10.3389","volume":"8","author":[{"given":"Deanna D.","family":"Dailey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit J.","family":"Bouma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn L.","family":"Duval","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"B1","volume-title":"Withrow and MacEwen's Small Animal Clinical Oncology","author":"Withrow","year":"2013"},{"key":"B2","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1186\/1471-2407-10-506","article-title":"Expression profiling in canine osteosarcoma: identification of biomarkers and pathways associated with outcome","volume":"10","author":"O'Donoghue","year":"2010","journal-title":"BMC Cancer."},{"key":"B3","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.cell.2009.06.016","article-title":"Widespread shortening of 3\u2032UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.","volume":"138","author":"Mayr","year":"2009","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1158\/0008-5472.CAN-08-0264","article-title":"Identification of let-7-regulated oncofetal genes","volume":"68","author":"Boyerinas","year":"2008","journal-title":"Cancer Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.cell.2012.04.005","article-title":"Roles for microRNAs in conferring robustness to biological processes","volume":"149","author":"Ebert","year":"2012","journal-title":"Cell."},{"key":"B7","doi-asserted-by":"publisher","first-page":"15524","DOI":"10.1073\/pnas.242606799","article-title":"Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia","volume":"99","author":"Calin","year":"2002","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/emmm.201100209","article-title":"MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review","volume":"4","author":"Iorio","year":"2012","journal-title":"EMBO Mol Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1261\/rna.1947110","article-title":"Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression","volume":"16","author":"Git","year":"2010","journal-title":"RNA."},{"key":"B10","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/bonekey.2014.44","article-title":"MicroRNAs as regulators of bone homeostasis and bone metastasis","volume":"3","author":"Ell","year":"2014","journal-title":"Bonekey Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"359739","DOI":"10.1155\/2012\/359739","article-title":"MicroRNA involvement in osteosarcoma","volume":"2012","author":"Kobayashi","year":"2012","journal-title":"Sarcoma."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.1007\/s11033-014-3193-7","article-title":"Epigenetic alterations in osteosarcoma: promising targets","volume":"41","author":"Li","year":"2014","journal-title":"Mol Biol Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/978-3-319-04843-7_6","article-title":"MicroRNAs in osteosarcomagenesis","volume":"804","author":"Kafchinski","year":"2014","journal-title":"Adv Exp Med Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.cca.2015.01.025","article-title":"MicroRNAs in osteosarcoma","volume":"444","author":"Zhang","year":"2015","journal-title":"Clin Chim Acta."},{"key":"B15","doi-asserted-by":"publisher","first-page":"877","DOI":"10.3390\/ijms17060877","article-title":"Involvement and clinical aspects of microRNA in osteosarcoma","volume":"17","author":"Ram Kumar","year":"2016","journal-title":"Int J Mol Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"19249","DOI":"10.1002\/jcp.28744","article-title":"Noncoding RNAs as circulating biomarkers in osteosarcoma patients","volume":"234","author":"Botti","year":"","journal-title":"J Cell Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1007\/s12094-019-02104-z","article-title":"miRNA signatures in childhood sarcomas and their clinical implications","volume":"21","author":"Viera","year":"2019","journal-title":"Clin Transl Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"100307","DOI":"10.1016\/j.jbo.2020.100307","article-title":"Potential diagnostic value of miRNAs in peripheral blood for osteosarcoma: a meta-analysis","volume":"23","author":"Guo","year":"2020","journal-title":"J Bone Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1158\/0008-5472.CAN-11-1460","article-title":"miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression","volume":"72","author":"Huang","year":"2012","journal-title":"Cancer Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cancergen.2012.03.001","article-title":"MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma","volume":"205","author":"Baumhoer","year":"2012","journal-title":"Cancer Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e48086","DOI":"10.1371\/journal.pone.0048086","article-title":"Modulation of the osteosarcoma expression phenotype by microRNAs","volume":"7","author":"Namlos","year":"2012","journal-title":"PLoS One."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.3892\/ol.2012.866","article-title":"Changes in microRNA expression in the MG-63 osteosarcoma cell line compared with osteoblasts","volume":"4","author":"Hu","year":"2012","journal-title":"Oncol Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1158\/0008-5472.CAN-11-2663","article-title":"miRNA signatures associate with pathogenesis and progression of osteosarcoma","volume":"72","author":"Jones","year":"2012","journal-title":"Cancer Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/1878-0261.12154","article-title":"miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts","volume":"12","author":"Andersen","year":"2018","journal-title":"Mol Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1007\/s12032-010-9563-7","article-title":"MicroRNA-21 is involved in osteosarcoma cell invasion and migration","volume":"28","author":"Ziyan","year":"2011","journal-title":"Med Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1003210","DOI":"10.1371\/journal.pcbi.1003210","article-title":"How microRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation","volume":"9","author":"Poos","year":"2013","journal-title":"PLoS Comput Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e00132","DOI":"10.1042\/BSR20140084","article-title":"MicroRNA-199a-3p and microRNA-34a regulate apoptosis in human osteosarcoma cells","volume":"34","author":"Tian","year":"2014","journal-title":"Biosci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"21307","DOI":"10.1074\/jbc.M112.445890","article-title":"MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma","volume":"288","author":"van der Deen","year":"2013","journal-title":"J Biol Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/gm406","article-title":"MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32","volume":"5","author":"Kelly","year":"2013","journal-title":"Genome Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1750-1172-8-7","article-title":"MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma","volume":"8","author":"Sarver","year":"2013","journal-title":"Orphanet J Rare Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.bone.2011.10.012","article-title":"Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma","volume":"50","author":"Thayanithy","year":"2012","journal-title":"Bone."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e102621","DOI":"10.1371\/journal.pone.0102621","article-title":"The tumor-suppressive microRNA-135b targets c-myc in osteoscarcoma","volume":"9","author":"Liu","year":"2014","journal-title":"PLoS One."},{"key":"B33","doi-asserted-by":"publisher","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.2353\/jmoldx.2008.070153","article-title":"Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues","volume":"10","author":"Doleshal","year":"2008","journal-title":"J Mol Diagn."},{"key":"B35","doi-asserted-by":"publisher","first-page":"415","DOI":"10.2353\/jmoldx.2008.080018","article-title":"Accurate molecular characterization of formalin-fixed, paraffin-embedded tissues by microRNA expression profiling","volume":"10","author":"Szafranska","year":"2008","journal-title":"J Mol Diagn."},{"key":"B36","first-page":"4194","article-title":"Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in patients with osteosarcoma","volume":"7","author":"Zhang","year":"2014","journal-title":"Int J Clin Exp Pathol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ymeth.2010.01.032","article-title":"Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR)","volume":"50","author":"Kroh","year":"2010","journal-title":"Methods."},{"key":"B40","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1186\/1756-0500-4-555","article-title":"A novel mean-centering method for normalizing microRNA expression from high-throughput RT-qPCR data","volume":"4","author":"Wylie","year":"2011","journal-title":"BMC Res Notes."},{"key":"B41","doi-asserted-by":"publisher","first-page":"W498","DOI":"10.1093\/nar\/gks494","article-title":"DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways.","volume":"40","author":"Vlachos","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"W460","DOI":"10.1093\/nar\/gkv403","article-title":"DIANA-miRPath v3.0: deciphering microRNA function with experimental support.","volume":"43","author":"Vlachos","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/1746-6148-9-130","article-title":"HES1, a target of Notch signaling, is elevated in canine osteosarcoma, but reduced in the most aggressive tumors","volume":"9","author":"Dailey","year":"2013","journal-title":"BMC Vet Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1586\/erm.09.25","article-title":"Current molecular diagnostics of breast cancer and the potential incorporation of microRNA","volume":"9","author":"Zoon","year":"2009","journal-title":"Expert Rev Mol Diagn."},{"key":"B46","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1111\/jvim.12313","article-title":"Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 dogs after amputation for treatment of appendicular osteosarcoma","volume":"28","author":"Selmic","year":"2014","journal-title":"J Vet Intern Med."},{"key":"B47","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.2460\/javma.1998.213.07.1002","article-title":"Prognostic importance of alkaline phosphatase activity in serum from dogs with appendicular osteosarcoma: 75 cases (1990-1996)","volume":"213","author":"Ehrhart","year":"1998","journal-title":"J Am Vet Med Assoc."},{"key":"B48","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1746-6148-8-56","article-title":"Prognostic factors in canine appendicular osteosarcoma - a meta-analysis","volume":"8","author":"Boerman","year":"2012","journal-title":"BMC Vet Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1354\/vp.39-2-240","article-title":"Prognostic significance of a new histologic grading system for canine osteosarcoma","volume":"39","author":"Kirpensteijn","year":"2002","journal-title":"Vet Pathol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jcpa.2006.11.005","article-title":"Clinicopathological relevance of tumour grading in canine osteosarcoma","volume":"136","author":"Loukopoulos","year":"2007","journal-title":"J Comp Pathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1177\/0300985817747329","article-title":"Histologic grade does not predict outcome in dogs with appendicular osteosarcoma receiving the standard of care","volume":"55","author":"Schott","year":"2018","journal-title":"Vet Pathol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1161\/CIRCULATIONAHA.111.087817","article-title":"A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation","volume":"125","author":"Zhuang","year":"2012","journal-title":"Circulation."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1038\/nature06607","article-title":"Regulation of progenitor cell proliferation and granulocyte function by microRNA-223","volume":"451","author":"Johnnidis","year":"2008","journal-title":"Nature."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.bbadis.2014.03.005","article-title":"miR-223: an inflammatory oncomiR enters the cardiovascular field","volume":"1842","author":"Taibi","year":"2014","journal-title":"Biochim Biophys Acta."},{"key":"B55","doi-asserted-by":"publisher","first-page":"4840","DOI":"10.1158\/0008-5472.CAN-10-0269","article-title":"Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses","volume":"70","author":"Wang","year":"2010","journal-title":"Cancer Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/jcb.21335","article-title":"MicroRNA-223 is a key factor in osteoclast differentiation","volume":"101","author":"Sugatani","year":"2007","journal-title":"J Cell Biochem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1476-4598-10-117","article-title":"Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells","volume":"10","author":"Yang","year":"2011","journal-title":"Mol Cancer."},{"key":"B58","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3389\/fphar.2018.00915","article-title":"Differentially tolerized mouse antigen presenting cells share a common miRNA signature including enhanced mmu-miR-223-3p expression which is sufficient to imprint a protolerogenic state","volume":"9","author":"Bros","year":"2018","journal-title":"Front Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1379458","DOI":"10.1155\/2020\/1379458","article-title":"miR-223-3p Inhibits antigen endocytosis and presentation and promotes the tolerogenic potential of dendritic cells through targeting mannose receptor signaling and Rhob","volume":"2020","author":"Tang","year":"2020","journal-title":"J Immunol Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S1535-6108(04)00081-9","article-title":"Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt\/PKB pathway","volume":"5","author":"Bao","year":"2004","journal-title":"Cancer Cell."},{"key":"B61","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/ijc.29376","article-title":"Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment","volume":"137","author":"Segaliny","year":"2015","journal-title":"Int J Cancer."},{"key":"B62","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3892\/ijo.2013.2164","article-title":"Antitumor activity of neurokinin-1 receptor antagonists in MG-63 human osteosarcoma xenografts","volume":"44","author":"Munoz","year":"2014","journal-title":"Int J Oncol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1158\/1078-0432.CCR-10-2047","article-title":"Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents","volume":"17","author":"Buddingh","year":"2011","journal-title":"Clin Cancer Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.2217\/imt.13.102","article-title":"Targeting tumor-infiltrating macrophages to combat cancer","volume":"5","author":"Panni","year":"2013","journal-title":"Immunotherapy."},{"key":"B65","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/978-3-319-04843-7_17","article-title":"Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) in the treatment of osteosarcoma","volume":"804","author":"Meyers","year":"2014","journal-title":"Adv Exp Med Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3390\/biology9110385","article-title":"Cytoskeletal remodeling in cancer","volume":"9","author":"Aseervatham","year":"2020","journal-title":"Biology"},{"key":"B67","first-page":"4993","article-title":"E-cadherin and alpha-catenin expression in normal, hyperplastic and neoplastic endometrium","volume":"30","author":"Carico","year":"2010","journal-title":"Anticancer Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1038\/ncomms3531","article-title":"Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas","volume":"4","author":"Fanjul-Fernandez","year":"2013","journal-title":"Nat Commun."},{"key":"B69","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1476-4598-7-35","article-title":"Potential role of miR-9 and miR-223 in recurrent ovarian cancer","volume":"7","author":"Laios","year":"2008","journal-title":"Mol Cancer."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.7150\/ijbs.5106","article-title":"Identification of metastamirs as metastasis-associated microRNAs in clear cell renal cell carcinomas","volume":"8","author":"Wotschofsky","year":"2012","journal-title":"Int J Biol Sci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13046-015-0145-6","article-title":"MiR-223 promotes the cisplatin resistance of human gastric cancer cells via regulating cell cycle by targeting FBXW7","volume":"34","author":"Zhou","year":"2015","journal-title":"J Exp Clin Cancer Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.biopha.2013.03.013","article-title":"MiR-223\/Ect2\/p21 signaling regulates osteosarcoma cell cycle progression and proliferation","volume":"67","author":"Xu","year":"2013","journal-title":"Biomed Pharmacother."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1016\/j.humpath.2014.02.018","article-title":"Prognostic value of microRNA-223\/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma","volume":"45","author":"Zhang","year":"2014","journal-title":"Hum Pathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1159\/000343336","article-title":"Heat shock protein 90B1 plays an oncogenic role and is a target of microRNA-223 in human osteosarcoma","volume":"30","author":"Li","year":"2012","journal-title":"Cell Physiol Biochem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4419-0284-9_1","article-title":"The epidemiology of osteosarcoma","volume":"152","author":"Ottaviani","year":"2009","journal-title":"Cancer Treat Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.3892\/ol.2018.9793","article-title":"Let-7b acts as a tumor suppressor in osteosarcoma via targeting IGF1R","volume":"17","author":"Zhang","year":"2019","journal-title":"Oncol Lett."},{"key":"B77","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.pharmthera.2012.09.003","article-title":"New targets and approaches in osteosarcoma","volume":"137","author":"Gill","year":"2013","journal-title":"Pharmacol Ther."},{"key":"B78","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bbrc.2012.12.118","article-title":"Inhibition of the Wnt-beta-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy","volume":"431","author":"Ma","year":"2013","journal-title":"Biochem Biophys Res Commun."},{"key":"B79","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.molonc.2014.02.009","article-title":"The validity of circulating microRNAs in oncology: five years of challenges and contradictions","volume":"8","author":"Jarry","year":"2014","journal-title":"Mol Oncol."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.637622\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T10:52:00Z","timestamp":1724842320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.637622\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":79,"alternative-id":["10.3389\/fvets.2021.637622"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.637622","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"article-number":"637622"}}