LncRNA-AK058003/miR-218信号通路调控胃癌侵袭转移机制研究

The invasion and metastasis of the gastric cancer(GC)cells is the main factor of patients' poor prognosis ,and the mechanism is still not clearly demonstrated. We identified and confirmed that lncRNA-AK058003 was a key molecule in promoting GC metastasis in our early study,but the mechanism is still not clear. The results of miRNA microarray and the expression examination in GC cell lines and tissues suggest that AK058003 could inhibit the expression of miR-218.Further bioinformatics analysis shows that there are several binding sites between them. Based on this, We hypothesize that AK058003 regulates the expression of miR-218 by acting as miRNA sponge.We will further conduct an in-depth study of the regulation mechanisms of miR-218 mediated by AK058003 using reporter gene assay ,R-IP, CHIP in this project. Screen the downstream effector molecules through the double limit of AK058003 and miR-218 using iTRAQ and gene microarray. In order to reveal the concrete mechanism that regulation of GC metastasis mediated by AK058003/miR-218/ downstream effector molecules signaling pathway.

胃癌细胞的侵袭转移是患者预后不良的主要因素，其机制尚不明确。我们在前期研究中，首次发现一个胃癌转移相关新lncRNA分子AK058003，并证实其在胃癌转移过程中发挥关键作用，但机制仍未阐明。miRNA芯片筛选验证和胃癌组织、细胞表达检测提示AK058003可以抑制miR-218表达，进一步生物信息学分析发现两者存在多个结合位点，基于此我们提出AK058003通过miRNA海绵作用调控miR-218的理论假说。本项目拟通过荧光素酶报告基因、R-IP、启动子甲基化、CHIP等技术进一步深入探讨AK058003调控miR-218的机制。通过表达谱芯片、iTRAQ 及生物信息学分析在AK058003、miR-218双重限定下筛选AK058003/miR-218下游效应分子并加以验证。以期揭示AK058003/miR-218/下游效应分子信号通路调控胃癌转移的具体机制，为胃癌转移的防治提供新思路。

胃癌细胞的侵袭转移是患者预后不良的主要因素，其机制尚不明确。获得胃癌转移发生的差异lncRNA，靶向lncRNA分子的干预能够更有效的预测和控制多因素、多基因变化的胃癌转移过程，在此项研究中我们首次发现胃癌转移相关新lncRNA分子AK058003、BC005927，并证实其在胃癌转移过程中发挥关键作用，并初步探讨了她们在影响肿瘤转移过程中所发挥的机制，为寻求逆转胃癌转移提供了新的策略和思路。