miR-377与胃癌复发转移预后的关系及其机制研究

Metastasis is the leading cause of gastric cancer treatment failure is metastasis. Emerging studies have implicated the role of miRNA on cancer metastasis. Our previous study revealed that miR-377 is overexpressed in metastatic lesions of gastric cancer, suggesting its potential role in cancer metastasis. Till now, the role of miR-377 in cancers other than prostate cancer and marginal lymphoma is still unclear. Our former study showed that miR-377 is overexpressed in gastric cancer cell lines and gastric tumors, and its expression correlates with advanced clinical stage, lymph node metastasis, and poor prognosis; overexpression of miR-377 promotes cell migration in gastric cancer cells. Thus our preliminary data suggested that miR-377 acts as a important inducer of cancer metastasis and might be an prognosis factor. The target screening assay for miR-377 revealed that CFTR, PPP3R1, PUM2, IL18R1 or RNF38 might be its direct downstream target gene. This purpose of this study is to investigate the role and mechanism of miR-377 in gastric cancer metastasis in cancer tissues, cancer cells and animal experiments. This study will better elucidate the molecular mechanisms for cancer metastasis from the angle of miRNA, and may provide available predictor for cancer metastasis and prognosis.

侵袭转移是导致中晚期胃癌患者治疗失败的主要原因。越来越多的证据表明miRNA通过调节下游靶基因参与肿瘤的侵袭转移。我们前期工作中发现胃癌转移灶中高表达miR-377，提示其可能参与肿瘤侵袭转移过程。除了前列腺癌及边缘区淋巴瘤以外，目前尚无miR-377与其它肿瘤的相关报道。预实验发现miR-377表达水平与胃癌浸润深度和淋巴结转移呈正相关，与预后呈负相关；miR-377可促进胃癌细胞体外迁移能力。提示miR-377在促胃癌转移中扮演重要角色，可能成为重要的预后预测因子。靶基因筛查发现CFTR、PPP3R1、PUM2、IL18R1及RNF38可能是其下游直接靶基因。本课题将从组织、细胞及动物三方面进一步验证miR-377在促胃癌转移中的作用，同时探索其对筛选出的下游靶基因的调控。本项目将从miRNA角度进一步阐明胃癌侵袭转移机制， 有望发现新的胃癌复发转移及预后预测因子。