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MiRNA expression profiles in the serum of Doberman Pinschers

ABSTRACT: Background: Dilated cardiomyopathy (DCM) is the most common acquired heart disease in large- and giant-breed dogs with Doberman Pinschers representing one of the most frequently affected breeds. MicroRNAs (miRNAs) are short non-coding RNAs which play important roles in gene regulation. Different miRNA expression patterns have been described for human DCM and might represent potential diagnostic markers. There are no studies to date investigating miRNA expression profiles in canine DCM. Goals: The goals of this study were to screen the miRNAs expression profile of canine serum by using a miRNA microarray platform and to compare the miRNA expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results: Although total RNA concentrations were very low in canine serum samples, 421 different miRNAs were detectable with sufficient signal intensity on the miRNA microarrays. About 30 miRNAs were differentially expressed in the two groups, but did not reach statistical significance. No significant differences were found using specific miRNA PCR assays. Conclusions: More than 400 miRNAs can be detected in canine serum samples. Changes in expression levels of various miRNAs between healthy and DCM dogs could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE36976 | GEO | 2013/03/22

SECONDARY ACCESSION(S): PRJNA157507

REPOSITORIES: GEO

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Project description:Mammary cancer is the most common type of cancer in female dogs with a lifetime risk of over 24% when dogs are not spayed. The elucidation of the complete canine genome opens new areas for development of cancer therapies. These should be tested first by in vitro models such as cell lines. However, to date, no canine mammary cell lines have been characterized by expression profiling. In this study, canine mammary tumour cell lines with histologically distinct primary tumours of origin were characterized using a newly developed canine cDNA microarray. Comparisons of gene expression profiles showed enrichment for distinct biological pathways and were related to biological properties of the cell lines such as growth rate and in vitro tumourigenicity. Additionally, gene expression profiles of cell lines also showed correspondence to their tumour of origin. Major differences were found in Wnt, cell cycle, cytokine/Rho-GTPase, alternative complement and integrin signalling pathways. Because these pathways show an overlap at the molecular level with those found in human breast cancer, the expression profiling of spontaneous canine mammary cancer may also function as a biological sieve to identify conserved gene expression or pathway profiles of evolutionary significance that are involved in tumourigenesis. These results are the basis for further characterization of canine mammary carcinomas and development of new therapies directed towards specific pathways. In addition these cell lines can be used to further investigate identified deregulated pathways and characterize until now unannotated genes. Keywords: cell line type comparision Three canine mammary tumor cell lines (CMT) originating from benign mixed tumor (CMT-U229), primary mammary osteosarcoma (CMT-U335) and primary mammary anaplastic carcinoma (P114) were compared directly to each other in this study. Total RNA was isolated from cells grown to near confluence. In vitro transcription followed by labeling and hybridization to cDNA microarray was carried out. In a loop design of hybridization, labeled cRNA from cell lines were hybridized against each other. Statistical analysis of the log transformed normalized data was done using SAM (significance analysis of microarray) and differentially expressed genes from each experimental subset (comparison of two cell lines) were identified. Dye swaps and at least one biological replicates were included under each experimental subset (each comparision).

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MiRNA expression profiles in the serum of Doberman Pinschers

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