中文摘要
环状RNA(circRNA)是一类5'末端和3'末端反向共价键结合的内源性RNA分子。前期研究发现circ_0000471具有良好的胃癌组织特异性和促癌作用,但其参与胃癌发生的机制未明。生物信息学预测及前期实验显示circ_0000471极有可能是以竞争性内源RNA(ceRNA)方式结合miR-135a-5p调控LATS2的表达,通过Wnt/β-catenin和Hippo信号通路促进胃癌发生的。为此,本研究以ceRNA为切入点,利用基因转染、RNA干扰、Western印迹、RNA结合蛋白免疫沉淀(RIP)、免疫组化等多种研究手段,从分子、细胞、组织和实验动物这4个水平探究circ_0000471是否以ceRNA方式调控LATS2促进胃癌发生,阐明circ_0000471促癌的下游分子机制,同时明确其用于胃癌筛查、分型、预后、复发转移预测的临床价值。本研究将为胃癌发病机制研究提供新思路。
英文摘要
Circular RNAs (circRNAs) are a special class of endogenous RNAs characterized by jointing 3’ and 5’ends reverse covalent together. Our previous studies have shown that circ_0000471 has good tissue specificity and tumor promoting effect, but its mechanisms in gastric carcinogenesis are unknown. Bioinformatics prediction and previous experiments showed that circ_0000471 is highly likely acting as competing endogenous RNA (ceRNA) in combination with miR-135a-5p to regulate LATS2 level in gastric carcinogenesis through Wnt/β-catenin and Hippo signaling pathway. Thus, taking ceRNA as the breakthrough point, we decide to use gene transfection, RNA interference, Western blot, RNA binding protein immunoprecipitation (RIP), immunohistochemistry and other methods to investigate whether circ_0000471 regulates LATS2 to promote gastric carcinogenesis by ceRNA, the molecular mechanism of circ_0000471 in carcinogenesis and its clinical value in gastric cancer screening, classification, prognosis, recurrence and metastasis from four levels of molecules, cells, tissues and animal experiments. Our study will provide new ideas for the study of the pathogenesis of gastric carcinogenesis.
