Functional analysis of differentially regulated microRNAs in the canine intestinal T-cell lymphoma

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Gastrointestinal lymphomas (tumors) are not uncommon in dogs. Most of these tumors are derived from specialized immune cells (T-cells). The prognosis is poor with a life expectancy under three months after diagnosis. Since non-tumorous gastrointestinal inflammation can induce similar clinical symptoms, the diagnosis is not straightforward.MicroRNAs belong to a class of short RNA molecules that influence the cell metabolism on several levels. By inhibiting gene expression they regulate cellular pathways like cell division, cell differentiation and programmed cell death. Enhanced or inhibited miRNA expression is associated with numerous diseases.In humans, several studies in lymphomas of different immune cells (B-cells) could already show marked changes in the expression of several microRNAs in the tumor tissue, which might include suitable candidates for tumor markers. Very little is known about the microRNA expression in human T-cell lymphomas.In dogs, studies about the microRNA expression in lymphomas are scarce and nothing is known about their significance in intestinal T-cell lymphomas and their influence on these tumor cells.The aim of this study is to characterize the influence of enhanced or inhibited microRNA expression on cells of a canine T-cell lymphoma. Several microRNAs have already been selected according to their differences in expression in normal gastrointestinal tissue, tissue displaying gastrointestinal inflammation, and gastrointestinal T-cell lymphomas. Molecules that either enhance or inhibit specific microRNAs are introduced into canine T-cell lymphoma cells, and the effects on cellular proliferation, cell death and protein expression are measured with appropriate tests. This may lead to new findings about the role of microRNAs in tumor development. They may also be possible therapeutic targets of T-cell lymphomas in dogs. Moreover, the spontaneously developing tumors of dogs are under scrutiny in studies about the effectiveness of new tumor therapeutics, which may benefit dogs and humans alike.