中文摘要
胃癌是最常见的消化系统肿瘤之一。最近,科学家们发现环状RNA比线性RNA更加稳定,并大量存在于真核细胞转录组中,具有临床诊断及预后标志物的潜在应用价值。我们前期对胃癌组织和癌旁正常组织进行了circRNA芯片检测,发现circVIL1在胃癌组织中表达显著上调。体外功能研究发现circVIL1 siRNA能抑制胃癌细胞的恶性增殖、侵袭和迁移能力。已知circRNA能够竞争性结合miRNA,抑制其对应mRNA的降解作用。前期研究发现circVIL1有miR-615-5p结合位点,能调控miR-615-5p表达。本研究在此基础上,阐明circVIL1在胃癌发生发展中的作用及circVIL1对下游miR-615-5p、靶基因的调控机制。同时,我们将检测大样本胃癌组织中circVIL1的表达,分析与临床病理特征及预后关系。本项目有望拓展对circRNA的认识,为寻找胃癌转移新的治疗靶标提供理论依据。
英文摘要
Gastric cancer (GC) is one of the most common digestive system tumors. Even with the opportunity to receive comprehensive treatment, the overall prognosis of gastric cancer is poor. Recently, scientists found that circular RNA (circRNA) molecules, rather than linear RNA molecules, are a common phenomenon in gene expression in human cells. It plays an important role in the development of many kinds of tumors. Previously we analyzed the expression profiles of circRNAs in advanced gastric adenocarcinoma tissues and adjacent normal mucosa tissues by biochips. We found that the expression of circVIL1 is significantly upregulated in GC tissues compared to adjacent normal mucosa tissues. In vitro assays showed that silencing of circVIL1 significantly suppressed GC cell proliferation, migration and invasion. Furtermore, bioinformatics and dual-luciferase analysis found that circVIL1 can combine competitively with miR-615-5p. On this basis, we will further investigate the functions of circVIL1, the possible mechaniam of miR-615-5p regulation by circVIL1 and the downstream target genes of miR-615-5p in GC. At the same time, we will detect the expression of circVIL1 in a large number of GC samples, analyze the relationship with clinical pathological characteristics and prognosis of patients. Our study will provide a new perspective on gastric cancer metastasis and recurrence and the findings of this study may contribute to the treatment and diagnosis of gastric cancer.
