tRF-5026a作为胃癌新型诊断标志物的价值及其作用机制研究

tRNA衍生片段(tRF)是在应激或疾病情况下，由RNA酶特异性切割tRNA所产生的非编码小RNA。tRF曾一度被认为是tRNA随机降解的产物，但近期发现，tRF具有组织特异性和疾病相关性，在肿瘤发生中发挥重要作用。因修饰丰富而结构稳定，突显tRF作为新型肿瘤标志物的优势。课题组最近筛选出一些胃癌相关tRF，并初步发现tRF-5026a可能通过调控PTEN/PI3K/AKT通路影响胃癌细胞生长。为此，本研究拟通过上调和下调胃癌细胞及正常胃黏膜上皮细胞中tRF-5026a的水平，先采用RNA免疫共沉淀和Western印迹等技术查明tRF-5026a如何调控PTEN/PI3K/AKT通路影响胃癌细胞生长；再经裸鼠实验明确其对胃癌细胞生长的影响；最后通过比较健康人、良性胃病、胃癌前病变、早期胃癌和晚期胃癌等5组人血浆tRF-5026a水平的变化规律，确定其诊断价值，希望提高胃癌的非创性诊断水平。

tRNA-derived fragments (tRFs) are small non-coding RNAs derived from tRNAs by the cleavage of RNases under stress or disease occurrence. Thought as tRNAs' random degradation products for several decades, however, recent studies found that tRFs have tissue specificity and disease association, and play important roles during carcinogenesis. There are lots of modifications in tRFs and these modifications make tRFs more stable. This characteristic highlights their advantages as novel tumor markers. Recently, our group screened some gastric cancer-associated tRFs and found that tRF-5026a regulated gastric cancer cell growth through PTEN/PI3K/AKT pathway. As a result, in this study, we will upregulate and downregulate the expression levels of tRF-5026a in gastric cancer cells and normal gastric epithelial cells. By RNA immunoprecipitation, Western blot and other technologies, we will first explore how tRF-5026a regulates PTEN/PI3K/AKT pathway to affect gastric cancer cell growth. Then the xenograft tumor experiment in nude mice will be used to confirm the results. Finally, through comparing the changes of the levels of tRF-5026a in plasma among health controls, patients with benign gastric diseases, gastric precancerous lesion, early gastric cancer, and advantaged gastric cancer, its diagnostic values will be analyzed. This study may improve the non-invasive diagnostic level of gastric cancer.