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To our knowledge, our study is the first to observe differential expression of miR-103b and miR-16 in urine samples from canine bladder cancer patients versus patients with LUTD. Decreased miR-103b expression has been observed in human patients with muscle-invasive bladder cancer (MIBC) and is associated with worse outcome , and dysregulation of miR-103b can result in altered expression of several molecules which play a role in carcinogenesis, for example, CCNE1, CDK2, CREB1, DICER, and PTEN  . Decreased miR-103b expression has also been shown to promote increased proliferation and invasiveness in colorectal cancer cell lines [8, 10, 11]. A role for miR-16 in bladder carcinogenesis, or differential expression of miR-16 in TCC, has not previously been reported, however, decreased expression of miR-16 is associated with chronic lymphocytic lymphoma (CLL) and prostate cancer [12-14]. The combined data support further investigation of miR-103b and miR-16 as potential biomarkers for both canine and human TCC.
Another key finding from our study is that loss of coordinated expression of some of the urine-derived miRNAs assessed, including miR-34a, occurs in canine TCC patients. MiR-34a is well known to be regulated by p53 and dysregulation of the p53 signaling axis is a hallmark of advanced TCC [15, 16]. While further analyses are needed to validate this preliminary finding, our data indicate analysis of multiple miRNAs and their relative expression to each other within each patient sample may be a promising strategy for TCC biomarker discovery studies.
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Ruth L. Vinall1, Michael Kent2, and Paramita M. Ghosh3
1. Department Pharmaceutical & Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA
2. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA
3. Department of Urology, University of California Davis, Sacramento, CA
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