MicroRNAs (miRNAs) are small non-coding RNAs that have been implicated in humans as having a fundamental role in cancer initiation and progression. Canine diffuse large B cell lymphoma (DLBCL) represents one of the most frequently encountered canine neoplasms. We hypothesized that canine DLBCL possess a unique miRNA expression signature and that miRNA dysregulation contributes to chemoresistance and prognosis.
In this study we confirmed that miRNAs in the dog are very similar to those in humans, i.e. are highly evolutionarily conserved, and that different miRNA analysis technologies that are applied to human cancers can be similarly applied to canine cancers. Furthermore, miRNA expression in healthy normal tissues is similar in dogs and humans. When we used “next generation” sequencing of canine DLBCL tumor samples to determine their miRNA expression profiles we identified a miRNA that was significantly overexpressed in chemotherapy naïve tumors compared to chemotherapy relapse tumors from the same patients. Significantly, this was a miRNA with known importance in human cancers. Additionally, we identified a unique miRNA expression signature (multiple coordinately expressed miRNAs) that was associated with overall survival in dogs with DLBCL and treated with a standard chemotherapy regimen. These findings provide insights into mechanisms of lymphomagenesis and potential targets for future therapies.
Co-sponsored with the AKC Canine Health Foundation, Grant Number: 00632
W. C. Kisseberth, DVM, PhD, Dip. ACVIM (Oncology)
Ohio State University