lncRNA-C21orF96/miR-875-5p/USF2调控轴介导胃癌淋巴管转移的机制

胃癌主要经淋巴结转移，其机制尚未完全阐明。我们前期发现lncRNA-C21orF96与胃癌淋巴转移和管形成相关；C21orF96抑制 miR-875-5p 表达，而miR-875-5p 直接靶向 USF2基因，参与 USF2 的表达调控，我们推测C21orF96 可能以“分子海绵”作用调控miR-875-5p/USF2 介导胃癌淋巴管的转移。本课题拟阐明C21orF96、miR-875-5p和USF2在胃癌组织、血液和转移灶中表达与胃癌病理特征和预后的关系；构建人高侵袭性胃癌淋巴管模型以明确C21orF96在胃癌和胃癌淋巴管形成的作用；以细胞和动物为模型探索C21orF96/miR-875-5p/USF2轴以“分子海绵”作用介导胃癌淋巴管转移的机制。通过上述研究明确lncRNA-C21orF96/miR-875-5p/USF2通路介导胃癌淋巴管转移的新机制，为胃癌治疗淋巴结转移提供新靶点。

Gastric cancer is mainly through lymph node metastasis, and the mechanism is not fully understood. In our previous study, we have found lncRNA-C21orF96 is associated with lymph node metastasis and tube formation. C21orF96 inhibits the expression of miR-875-5p, however, miR-875-5p targets USF2 gene, C21orF96 is involved with the regulation of USF2 gene. We speculate that lncRNA-C21orF96 regulates the lymphatic metastasis of gastric cancer by regulating miR-875-5p/USF2 via "Molecular sponge" function. In this study, we demonstrate the expression of C21orF96, miR-875-5p and USF2 in cancer tissues, blood and metastatic node of patients with gastric pathology, and their relationship with metastases associated characteristics and prognosis; we will try to construct a malignant lymphangiogenesis model to verify the function of lncRNA-C21orF96 in human gastric cancer and the lymphangiogenesis of gastric cancer; we explore the mechanisms of lncRNA-C21orF96/miR-875-5p/USF2 axis in the lymphatic metastasis of gastric cancer via “molecular sponge ”function using cell and animal models. In general, we hope to clarify the new mechanisms of LncRNA-C21orF96 in lymph metastases by miR-875-5p/USF2 pathway, and provide new target for the therapeutic interventions of gastric cancer with metastatic lymph nodes.