Malignancy Associated MicroRNA Expression Changes in Canine Mammary Cancer of Different Malignancies

MicroRNA has been suspected to be generally involved in carcinogenesis since their first description. A first study supported this assumption for canine mammary tumors when miRNA expression was compared to normal gland. The present study extends these results by comparing the expression of 16 microRNA (miRNA) and 4 small nucleolar RNA (snoRNA) in tumors of different malignancy, for example, adenomas, nonmetastasizing and metastasizing carcinomas as well as lymph node metastases, with each other and with normal mammary gland. All neoplastic tissues differed in their miR-210 expression levels from normal gland. While metastatic cells differed in their expression of mir-29b, miR-101, mir-125a, miR-143, and miR-145 from primary tumors, the comparison of miRNA expression in primary tumors of different malignancy failed to reveal significant differences except for a significant downregulation of mir-125a in metastasizing carcinomas when compared to adenomas. 1. Introduction MicroRNA (miRNA) is an evolutionarily conserved, noncoding, but regulatory RNA species of approximately 22 nucleotides in length. It plays a crucial role in various physiological and pathological processes by regulating gene expression posttranscriptionally. miRNA binds to messenger RNA (mRNA) and thereby induces a sequence-depending mRNA degradation or translational repression [1–3]. A deregulation of miRNA is associated with a wide variety of pathologic states including carcinogenesis [4]. Nevertheless, in many cases the specific function of individual miRNA species is still unknown. For instance, miR-10b has been identified as a tumor suppressor which prevents human breast cancer development but also as an oncogene which initiates breast cancer invasion and metastasis [5]. Several miRNA species have been identified to be involved in human breast cancer development including miR-21, miR-145, and miR-210 [6–8]. In veterinary medicine, only a single study is available on miRNA expression in canine mammary tumors. Boggs et al. [7] compared the expression levels of ten miRNA species in malignant mammary tumors and normal canine mammary gland and found a significant deregulation of miR-21, miR-29b, let-7f, miR-15a, and miR-16 in the tumors. In the present study, we expand these recent findings on the impact of miRNA deregulation on canine mammary tumors by asking for differences in expression levels of four small nucleolar RNA (snoRNA) and 16 canine miRNA with known relevance for human and canine mammary tumor development in tissue samples of normal mammary gland, adenomas, metastasizing, and