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

犬肠道T细胞淋巴瘤中差异调节的microRNA的功能分析

• 批准号: 399128212
• 负责人: Privatdozentin Dr. Karin Weber
• 金额: --
• 依托单位: Medizinische Kleintierklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/399128212?language=en
• 关键词: Functional; analysis; differentially; regulated; microRNAs

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.

胃肠道淋巴瘤（肿瘤）在狗中并不罕见。大多数这些肿瘤源自专门的免疫细胞（T 细胞）。预后很差，诊断后预期寿命不到三个月。由于非肿瘤性胃肠道炎症可诱发类似的临床症状，因此诊断并不简单。MicroRNA 属于一类短 RNA 分子，可在多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途径。 miRNA 表达的增强或抑制与多种疾病相关。在人类中，针对不同免疫细胞（B 细胞）的淋巴瘤的几项研究已经显示肿瘤组织中几种 microRNA 表达的显着变化，这可能包括合适的肿瘤标志物候选者。关于人类 T 细胞淋巴瘤中的 microRNA 表达知之甚少。在狗中，关于淋巴瘤中 microRNA 表达的研究很少，并且对其在肠道 T 细胞淋巴瘤中的意义及其对这些肿瘤细胞的影响一无所知。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。根据正常胃肠道组织、显示胃肠道炎症的组织和胃肠道T细胞淋巴瘤中表达的差异，已经选择了几种microRNA。将增强或抑制特定 microRNA 的分子引入犬 T 细胞淋巴瘤细胞中，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。这可能会带来关于 microRNA 在肿瘤发展中的作用的新发现。它们也可能是狗 T 细胞淋巴瘤的可能治疗靶点。此外，关于新肿瘤疗法有效性的研究正在仔细审查狗自发形成的肿瘤，这可能对狗和人类都有好处。