eIF6调控miR-21/PDCD4/MTA1通路促进结直肠癌侵袭转移及机制研究

MTA1是第一个被确定与肿瘤转移密切相关的基因，但其在结直肠癌（CRC）中的促肿瘤机制有待研究。申请人长期进行真核翻译起始因子（eIF）家族的研究并报道EIF5A2对MTA1具有重要的调控作用，然而其他eIF成员是否有此功能尚不清楚。我们前期发现eIF6可促进CRC的增殖及转移，但机制不明。有研究表明miR-21/PDCD4与MTA1可促进CRC细胞EMT并下调E-cad，而E-cad是EMT的标志物。因此推测，eIF6调控miR-21/PDCD4/MTA1通路促进CRC细胞EMT进而促进肿瘤增殖转移。我们运用FCM，WB，激光共聚焦，免疫荧光，基因工程等研究⑴CRC中eIF6对miR-21/PDCD4/MTA1通路的调控⑵miR-21/PDCD4与MTA1的相互作用及其对CRC增殖转移的影响⑶体内外实验证实eIF6促进CRC EMT及肿瘤转移。本研究将为结直肠癌防治提供新思路和新靶点。

MTA1 is the first tumor metastasis-related gene, however, the mechanism for its role in promoting tumour is still unclear. We have studied eIFs for a long term and reported that EIF5A2 could regulate MTA1 in colorectal carcinoma(CRC), but whether other family members function like EIF5A2 is not known. We found that eIF6 promted the proliferation and metastasis of CRC, the mechanism needs further research. In additon, there are reports which revealed miR-21/PDCD4 and MTA1 promoted EMT and down regulated E-cad---a marker for EMT, in CRC. Therefore, we hypothesized that eIF6 could regulate miR-21/PDCD4/MTA1 pathway to promote EMT and tumor proliferation and metastasis. We planned to study the following aspects by FCM, Western blot, CLSM, immunohistochemistry and gene clone technology: ⑴eIF6 regulates miR-21/PDCD4/MTA1 pathway in CRC ⑵the interregulation of miR-21/PDCD4 and MTA1 in CRC and its influnce on CRC proliferation and metastasis ⑶eIF6 regulates MTA1 to promote EMT and metastasis by in vivo and vitro experiments。This project will provide new methods and target for CRC prevention and therapy.