miR-1307-3p通过抑制IGFBP5影响胃癌发生发展的研究

Gastric cancer is one of the most common malignancies in China. microRNAs have been reported to play pivotal roles in development and progression of gastric cancer. In order to search more microRNAs involved in gastric carcinogenesis, we downloaded and analyzed microRNAs data of stomach adenocarcinoma from TCGA (the Gancer Genome Atlas). We observe that miR-1307-3p is upregulated in cancer tissue than that of normal gastric tissue, and gastric cancer patients with higher miR-1307-3p levels tend to have shorter lifespans. Moreover, this trend is also observed in our gastric cancer cohort. The tumor suppressor IGFBP5 is predicted to be a target of miR-1307-3p when combining results from RNAseq data and microRNAs target prediction. Based on these findings, we hypothesize that miR-1307-3p could promote gastric cancer via inhibiting IGFBP5. We will verify this hypothesis in gastric cancer patients, mouse model and gastric cancer cell lines. MiR-1307-3p level will be determined and compared in cancerous tissue and paired normal tissue from gastric cancer patients, and their associations with clinical parameters or overall survival will also be analyzed. MiR-1307-3p expression will be artificially up and down in gastric cancer cell lines and the influences will be evaluated on the ability of cell proliferation, apoptosis, migration and invasion. Nude mouse inoculated with cell lines forcing miR-1307-3p up or down will be raised and the xenografts will be assessed periodically. We will also explore whether miR-1307-3p promote gastric cancer via targeting tumor suppressor IGFBP5. Our research will add our understandings on the pathogenesis of gastric cancer and provides a new potential molecular target of treatment.

胃癌是严重影响居民健康的恶性肿瘤之一。microRNAs在胃癌发生发展中起重要作用。前期TCGA数据分析发现，miR-1307-3p在胃癌中表达升高，且高表达的患者生存时间有缩短趋势；在我们的胃癌人群中也呈现相同趋势。结合基因表达和生物信息学预测，发现抑癌基因IGFBP5可能是miR-1307-3p的靶基因。基于前期发现，我们认为miR-1307-3p通过抑制IGFBP5促进胃癌的发生发展。本项目拟在人群，动物和细胞三个水平上，比较已建立的胃癌队列中胃癌组织和正常胃黏膜中miR-1307-3p表达的差异，及不同表达水平与胃癌进展和生存的关系；检测miR-1307-3p过表达或敲除后对胃癌细胞增殖、凋亡、侵袭转移以及对小鼠移植瘤生长的影响；并探讨miR-1307-3p是否通过IGFBP5发挥上述作用，以明确miR-1307-3p在胃癌发生、发展和预后中的作用及机制，为胃癌的防治提供科学依据。

胃癌是严重影响居民健康的恶性肿瘤之一。microRNAs在胃癌发生发展中起重要作用。本项目研究了miR-1307-3p在胃癌发生发展和预后中的作用。研究结果显示，miR-1307-3p与胃癌相关。胃癌患者外周血血浆中miR-1307-3p表达水平升高，且表达水平与胃癌患者癌旁正常组织中的表达水平正相关，但与肿瘤组织的表达水平无相关性，显示miR-1307-3p有可能作为胃癌筛查的标志物，但需要更多研究阐明外周血中miR-1307-3p的来源。组织中miR-1307-3p表达水平检测显示，肿瘤组织中的表达水平低于正常组织，但是表达水平与患者进展和预后无关。细胞学实验显示，过表达miR-1307-3p的细胞增殖活性减弱。高通量测序、生物信息学分析和双荧光素酶报告基因实验显示ZNF350可能是miR-1307-3p的靶基因。本研究的结果显示，miR-1307-3p可能与胃癌的发生相关，但与胃癌的进展和预后无关，miR-1307-3p有可能作为胃癌筛查或诊断的标志物。