{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:39:27Z","timestamp":1780058367116,"version":"3.54.0"},"reference-count":63,"publisher":"American Veterinary Medical Association (AVMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To determine expression of microRNA (miRNA) in urinary bladder samples obtained from dogs with grossly normal urinary bladders, inflammatory bladder disease, or transitional cell carcinoma (TCC) and in cells of established canine TCC cell lines.<\/jats:p>\n<jats:p><jats:bold>Sample<\/jats:bold>\u2014Samples of grossly normal bladders (n = 4) and bladders from dogs with inflammatory bladder disease (13) or TCC (18), and cells of 5 established canine TCC cell lines.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Expression of 5 miRNAs (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) that target p53, Rb, or Bcl-2 protein pathways was determined for bladder samples and cells via quantitative real-time PCR assay. Effects of cisplatin (5\u03bcM) on proliferation and miRNA expression of cells were determined.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Expression of miR-34a and miR-106b was significantly higher in TCC samples than it was in samples of grossly normal bladders. Expression of miR-34a, miR-16, miR-103b, and miR-106b was higher in TCC samples than it was in bladder samples from dogs with inflammatory bladder disease. Cells of established canine TCC cell lines that had the lowest growth after cisplatin treatment had increased miR-34a expression after such treatment.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Findings of this study indicated results of miRNA expression assays can be used to distinguish between samples of grossly normal bladders and bladders of dogs with inflammatory bladder disease or TCC. This finding may have clinical relevance because currently available diagnostic tests cannot be used to differentiate these tissues, and inflammatory bladder disease and TCC are both prevalent in dogs. Validation of miRNA expression assays as diagnostic tests may be warranted.<\/jats:p>","DOI":"10.2460\/ajvr.73.10.1626","type":"journal-article","created":{"date-parts":[[2012,9,27]],"date-time":"2012-09-27T04:50:39Z","timestamp":1348721439000},"page":"1626-1633","source":"Crossref","is-referenced-by-count":29,"title":["Expression of microRNAs in urinary bladder samples obtained from dogs with grossly normal bladders, inflammatory bladder disease, or transitional cell carcinoma"],"prefix":"10.2460","volume":"73","author":[{"given":"Ruth L.","family":"Vinall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph W.","family":"deVere White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1939-1676.1992.tb00330.x","article-title":"Canine bladder and urethral tumors: a retrospective study of 115 cases (1980\u20131985)","volume":"6","author":"Norris","year":"1992"},{"key":"ref2","series-title":"Natl Cancer Inst Monogr","first-page":"1","article-title":"The occurrence of tumors in domestic animals","volume":"54","author":"Priester","year":"1980"},{"key":"ref3","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/j.1939-1676.2003.tb02424.x","article-title":"Canine transitional cell carcinoma","volume":"17","author":"Mutsaers","year":"2003"},{"key":"ref4","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.2460\/javma.2004.224.1290","article-title":"Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers","volume":"224","author":"Glickman","year":"2004"},{"key":"ref5","series-title":"J Toxicol Environ Health","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1080\/15287398909531360","article-title":"Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs","volume":"28","author":"Glickman","year":"1989"},{"key":"ref6","series-title":"TNM classification of tumours in domestic animals","first-page":"32","author":"Owen","year":"1980"},{"key":"ref7","series-title":"Urol Oncol","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S1078-1439(99)00006-X","article-title":"Naturally-occurring canine transitional cell carcinoma of the urinary bladder A relevant model of human invasive bladder cancer","volume":"5","author":"Knapp","year":"2000"},{"key":"ref8","series-title":"Vet Comp Oncol","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/j.1476-5810.2005.00070.x","article-title":"Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder","volume":"3","author":"Boria","year":"2005"},{"key":"ref9","series-title":"J Am Vet Med Assoc","first-page":"1588","article-title":"Cisplatin treatment of transitional cell carcinoma of the urinary bladder in dogs: 18 cases (1983\u20131993)","volume":"209","author":"Chun","year":"1996"},{"key":"ref10","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.2460\/javma.231.7.1056","article-title":"Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder","volume":"231","author":"Greene","year":"2007"},{"key":"ref11","series-title":"Mol Cancer Ther","first-page":"183","article-title":"Effects of the cyclooxygenase inhibitor, piroxicam, in combination with chemotherapy on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer","volume":"2","author":"Mohammed","year":"2003"},{"key":"ref12","series-title":"J Am Vet Med Assoc","first-page":"1530","article-title":"Cisplatin for treatment of transitional cell and squamous cell carcinomas in dogs","volume":"193","author":"Shapiro","year":"1988"},{"key":"ref13","series-title":"J Am Anim Hosp Assoc","doi-asserted-by":"publisher","first-page":"131","DOI":"10.5326\/0400131","article-title":"Piroxicam, mitoxantrone, and coarse fraction radiotherapy for the treatment of transitional cell carcinoma of the bladder in 10 dogs: a pilot study","volume":"40","author":"Poirier","year":"2004"},{"key":"ref14","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"549","DOI":"10.2460\/javma.228.4.549","article-title":"Evaluation of carbon dioxide laser ablation combined with mitoxantrone and piroxicam treatment in dogs with transitional cell carcinoma","volume":"228","author":"Upton","year":"2006"},{"key":"ref15","series-title":"Vet Surg","first-page":"450","article-title":"Vulvovaginectomy and perineal urethrostomy for neoplasms of the vulva and vagina","volume":"18","author":"Bilbrey","year":"1989"},{"key":"ref16","series-title":"Curr Urol Rep","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1007\/s11934-004-0040-8","article-title":"Screening for prostate cancer: updated experience from the Tyrol study","volume":"5","author":"Horninger","year":"2004"},{"key":"ref17","series-title":"Prim Care","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.pop.2010.05.001","article-title":"Prostate-specific antigen testing and prostate cancer screening","volume":"37","author":"Djavan","year":"2010"},{"key":"ref18","series-title":"AJR Am J Roentgenol","doi-asserted-by":"publisher","first-page":"303","DOI":"10.2214\/AJR.10.5815","article-title":"Colorectal cancer screening in women: an underutilized lifesaver","volume":"196","author":"Chu","year":"2011"},{"key":"ref19","series-title":"Cancer","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1002\/cncr.24760","article-title":"Annual report to the nation on the status of cancer, 1975\u20132006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates","volume":"116","author":"Edwards","year":"2010"},{"key":"ref20","series-title":"Ann Intern Med","doi-asserted-by":"publisher","first-page":"727","DOI":"10.7326\/0003-4819-151-10-200911170-00009","article-title":"Screening for breast cancer: an update for the US Preventive Services Task Force","volume":"151","author":"Nelson","year":"2009"},{"key":"ref21","series-title":"Vet Clin North Am Small Anim Pract","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0195-5616(03)00032-9","article-title":"Management of transitional cell carcinoma","volume":"33","author":"Henry","year":"2003"},{"key":"ref22","series-title":"Cornell Vet","first-page":"263","article-title":"Presumptive subcutaneous surgical transplantation of a urinary bladder transitional cell carcinoma in a dog","volume":"79","author":"Anderson","year":"1989"},{"key":"ref23","series-title":"Schweiz Arch Tierheilkd","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1024\/0036-7281.149.7.314","article-title":"Needle tract implantation after fine needle aspiration biopsy (FNAB) of transitional cell carcinoma of the urinary bladder and adenocarcinoma of the lung","volume":"149","author":"Vignoli","year":"2007"},{"key":"ref24","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.2460\/ajvr.2003.64.1017","article-title":"Evaluation of a bladder tumor antigen test as a screening test for transitional cell carcinoma of the lower urinary tract in dogs","volume":"64","author":"Henry","year":"2003"},{"key":"ref25","series-title":"Mol Ther","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1038\/sj.mt.6300311","article-title":"MicroRNAs in disease and potential therapeutic applications","volume":"15","author":"Soifer","year":"2007"},{"key":"ref26","series-title":"Nature","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/nature03441","article-title":"Systematic discovery of regulatory motifs in human promoters and 3\u2032 UTRs by comparison of several mammals","volume":"434","author":"Xie","year":"2005"},{"key":"ref27","series-title":"APMIS","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1111\/j.1600-0463.2007.apm_775.xml.x","article-title":"MicroRNAs and cancer","volume":"115","author":"Cowland","year":"2007"},{"key":"ref28","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1073\/pnas.0307323101","article-title":"Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers","volume":"101","author":"Calin","year":"2004"},{"key":"ref29","series-title":"Semin Cancer Biol","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2006.10.004","article-title":"MicroRNAs and genomic instability","volume":"17","author":"Huppi","year":"2007"},{"key":"ref30","series-title":"Int J Cancer","first-page":"953","article-title":"MicroRNA and cancer: current status and prospective","volume":"120","author":"Wu","year":"2007"},{"key":"ref31","series-title":"Nat Rev Cancer","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/nrc1997","article-title":"MicroRNA signatures in human cancers","volume":"6","author":"Calin","year":"2006"},{"key":"ref32","series-title":"Cancer Sci","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1111\/j.1349-7006.2007.00531.x","article-title":"Synergistic action of the microRNA-17 polycistron and Myc in aggressive cancer development","volume":"98","author":"Tagawa","year":"2007"},{"key":"ref33","series-title":"Oncogene","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1038\/sj.onc.1210083","article-title":"miR-21-mediated tumor growth","volume":"26","author":"Si","year":"2007"},{"key":"ref34","series-title":"Cell","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.cell.2006.02.037","article-title":"A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors","volume":"124","author":"Voorhoeve","year":"2006"},{"key":"ref35","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/ng.2007.30","article-title":"Widespread microRNA repression by Myc contributes to tumorigenesis","volume":"40","author":"Chang","year":"2008"},{"key":"ref36","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"20350","DOI":"10.1073\/pnas.0706901104","article-title":"MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression","volume":"104","author":"Lee","year":"2007"},{"key":"ref37","series-title":"Proc Natl Acad Sci U S A","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"},{"key":"ref38","series-title":"Nature","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nature03552","article-title":"A microRNA polycistron as a potential human oncogene","volume":"435","author":"He","year":"2005"},{"key":"ref39","series-title":"Int J Cancer","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1002\/ijc.26256","article-title":"MiR-34 chemosensitizes bladder cancer cells to cisplatin regardless of p53-Rb pathway status","volume":"130","author":"Vinall","year":"2012"},{"key":"ref40","series-title":"DNA Cell Biol","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1089\/dna.2006.0554","article-title":"miRNA profiling for diagnosis and prognosis of human cancer","volume":"26","author":"Jay","year":"2007"},{"key":"ref41","series-title":"Nat Methods","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nmeth717","article-title":"Microarray-based, high-throughput gene expression profiling of microRNAs","volume":"1","author":"Nelson","year":"2004"},{"key":"ref42","series-title":"Methods","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ymeth.2007.10.008","article-title":"In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations","volume":"44","author":"Nuovo","year":"2008"},{"key":"ref43","series-title":"BMC Biotechnol","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1472-6750-7-36","article-title":"Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells","volume":"7","author":"Li","year":"2007"},{"key":"ref44","series-title":"Nature","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA expression profiles classify human cancers","volume":"435","author":"Lu","year":"2005"},{"key":"ref45","series-title":"Cancer Chemother Pharmacol","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1007\/BF00686255","article-title":"Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors","volume":"29","author":"Knapp","year":"1992"},{"key":"ref46","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/j.1939-1676.1994.tb03232.x","article-title":"Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder","volume":"8","author":"Knapp","year":"1994"},{"key":"ref47","series-title":"Urol Oncol","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.urolonc.2008.02.015","article-title":"Canine invasive transitional cell carcinoma cell lines: in vitro tools to complement a relevant animal model of invasive urinary bladder cancer","volume":"27","author":"Dhawan","year":"2009"},{"key":"ref48","series-title":"Biotechnol Lett","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1007\/s10529-010-0380-z","article-title":"Normalization strategies for microRNA profiling experiments: a \u2018normal\u2019 way to a hidden layer of complexity?","volume":"32","author":"Meyer","year":"2010"},{"key":"ref49","series-title":"Methods","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001"},{"key":"ref50","series-title":"Mamm Genome","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00335-008-9128-7","article-title":"MicroRNA expression in canine mammary cancer","volume":"19","author":"Boggs","year":"2008"},{"key":"ref51","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"9136","DOI":"10.1073\/pnas.0508889103","article-title":"MicroRNAs exhibit high frequency genomic alterations in human cancer","volume":"103","author":"Zhang","year":"2006"},{"key":"ref52","series-title":"Cancer Res","doi-asserted-by":"publisher","first-page":"7065","DOI":"10.1158\/0008-5472.CAN-05-1783","article-title":"MicroRNA gene expression deregulation in human breast cancer","volume":"65","author":"Iorio","year":"2005"},{"key":"ref53","series-title":"Mol Cancer","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1476-4598-5-24","article-title":"Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies","volume":"5","author":"Mattie","year":"2006"},{"key":"ref54","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1073\/pnas.0510565103","article-title":"A microRNA expression signature of human solid tumors defines cancer gene targets","volume":"103","author":"Volinia","year":"2006"},{"key":"ref55","series-title":"RNA","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1261\/rna.1034808","article-title":"MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis","volume":"14","author":"Yan","year":"2008"},{"key":"ref56","series-title":"J Cell Physiol","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/jcp.20282","article-title":"miR-15a and miR-16\u20131 down-regulation in pituitary adenomas","volume":"204","author":"Bottoni","year":"2005"},{"key":"ref57","series-title":"Mol Cell Biochem","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s11010-011-0755-z","article-title":"miR-29b regulates migration of human breast cancer cells","volume":"352","author":"Wang","year":"2011"},{"key":"ref58","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1038\/nm.1880","article-title":"The miR-15a-miR-16\u20131 cluster controls prostate cancer by targeting multiple oncogenic activities","volume":"14","author":"Bonci","year":"2008"},{"key":"ref59","series-title":"Cancer Biol Ther","first-page":"1224","article-title":"MicroRNA-21: a novel therapeutic target in human cancer","volume":"10","author":"Pan","year":"2011"},{"key":"ref60","series-title":"Mol Cancer","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/1476-4598-6-60","article-title":"OncomiRs: the discovery and progress of microRNAs in cancers","volume":"6","author":"Cho","year":"2007"},{"key":"ref61","series-title":"Cancer Res","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1158\/0008-5472.CAN-10-2435","article-title":"miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 protooncogene in human invasive breast cancer","volume":"71","author":"Zhang","year":"2011"},{"key":"ref62","series-title":"Cell Death Differ","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/cdd.2009.56","article-title":"The miR-34 family in cancer and apoptosis","volume":"17","author":"Hermeking","year":"2010"},{"key":"ref63","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e18388","DOI":"10.1371\/journal.pone.0018388","article-title":"Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy","volume":"6","author":"Mizuno","year":"2011"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/73\/10\/ajvr.73.10.1626.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/73\/10\/ajvr.73.10.1626.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/73\/10\/ajvr.73.10.1626.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:29:04Z","timestamp":1741350544000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/73\/10\/ajvr.73.10.1626.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":63,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.73.10.1626","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2012,10]]}}}