MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours

Abstract

BackgroundMicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans.MethodsExpression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase.ResultsResults of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor.ConclusionsThe most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3751-1) contains supplementary material, which is available to authorized users.

CirculatingmicroRNAas biomarkers of canine mammary carcinoma in dogs

“…miR‐126 and miR‐214 both are significantly increased in dogs with mammary carcinoma (along with a number of other malignancies) relative to healthy controls 12 . Malignant CMT tissues show differential miRNA expression by grade and metastasis, but the proposed miRNAs of interest did not significantly differ in plasma 13 . A recent in vitro study demonstrated that CMT cells secrete exosomes enriched in miRNAs which could be released into blood, and that the exosomal miRNA pattern is predicted to regulate the estrogen receptor (ESR1), key tumor suppressor PTEN, and other genes relevant to human and canine mammary cancer 14 .…”

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

“…Thus, this approach heavily complicates the correct attribution of observed changes either to the cancer cells or to the stromal cells. To date, most studies investigating CMT on a molecular level, such as by sequencing or microarray analysis, have analyzed tumor tissue in bulk (e.g., Uva et al, 2009;Klopfleisch et al, 2010Klopfleisch et al, , 2011Liu et al, 2015;Bulkowska et al, 2017). Accordingly, specific analysis of CAS in CMTs has thus far been restricted to just single markers that were analyzed predominantly through immunohistochemistry (IHC).…”

MicroRNA and cancer: a focus on mammary tumors in female dogs

“…Studies on miRNAs in canine mammary tumors are scarce, particularly regarding metastatic progression (BULKOWSKA et al, 2017). Few studies have investigated the global miRNA expression profile in in vitro models of canine breast cancer (KRÓL et al, 2014;LUTFUL et al, 2015;OSAKI et al, 2016).…”

“…Few studies have investigated the global miRNA expression profile in in vitro models of canine breast cancer (KRÓL et al, 2014;LUTFUL et al, 2015;OSAKI et al, 2016). Some studies evaluated miRNA expression in different phases of tumorigenesis using canine breast tissue and reported several differentially expressed miRNAs (BOGGS et al, 2008;VON DEETZEN et al, 2014;BULKOWSKA et al, 2017).…”