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

胃肠道淋巴瘤（肿瘤）在狗身上并不罕见。这些肿瘤大多来源于特化的免疫细胞（t细胞）。预后很差，诊断后的预期寿命不到三个月。由于非肿瘤性胃肠道炎症可引起类似的临床症状，因此诊断并不简单。MicroRNAs属于一类短RNA分子，在几个层面上影响细胞代谢。通过抑制基因表达，它们调节细胞分裂、细胞分化和程序性细胞死亡等细胞通路。miRNA表达的增强或抑制与许多疾病有关。在人类中，对不同免疫细胞（b细胞）淋巴瘤的几项研究已经显示出肿瘤组织中几种microrna表达的显著变化，其中可能包括肿瘤标记物的合适候选物。目前对人类t细胞淋巴瘤中microRNA的表达知之甚少。在犬类中，关于microRNA在淋巴瘤中的表达的研究很少，对其在肠t细胞淋巴瘤中的意义及其对这些肿瘤细胞的影响尚不清楚。本研究的目的是表征增强或抑制microRNA表达对犬t细胞淋巴瘤细胞的影响。根据在正常胃肠道组织、胃肠道炎症组织和胃肠道t细胞淋巴瘤中的表达差异，已经选择了几种microrna。将增强或抑制特定microrna的分子引入犬t细胞淋巴瘤细胞，并通过适当的测试测量对细胞增殖、细胞死亡和蛋白质表达的影响。这可能会导致关于microrna在肿瘤发展中的作用的新发现。它们也可能是狗t细胞淋巴瘤的治疗靶点。此外，在研究新的肿瘤治疗方法的有效性时，狗的自发发展的肿瘤正在受到审查，这可能对狗和人类都有好处。

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.