miR-23a和miR-410在Fas通路诱导大肠癌EMT过程中的作用机制

申请人前期研究证实：Fas通路激活ERK1/2 并诱导上皮间质转换(EMT)从而促进大肠癌细胞迁移侵袭。预实验结果提示：Fas通路通过ERK1/2上调miR-23a和下调miR-410的表达，miR-23a上调和miR-410下调可能分别抑制E-cadherin和增强Snail的表达，从而促进EMT的发生。因此，申请人推测：Fas通路激活引起miR-23a和miR-410等表达的改变， miR-23a和miR-410参与调节EMT分子的表达从而促进大肠癌细胞EMT。本次研究主要探索：ERK1/2是否通过c-Fos/AP-1和NFAT4促进miR-23a的表达；miR-23a和miR-410是否可以分别抑制E-cadherin和Snail的表达；miR-23a和miR-410能否作为治疗靶点抑制Fas通路诱导的大肠癌转移。此次研究成果可为大肠癌的诊断标记物、治疗和预后分析提供新的分子靶点。

Our previous study confirmed that Fas signaling could induce EMT in colorectal cancer(CRC) by ERK1/2 MAPK activation. Preliminary data indicates Fas signaling enhances miR-23a and inhibits miR-410 in expression by ERK1/2 activation, and upregualtion of miR-23a may inhibit E-cadherin while downregulation of miR-410 may enhance Snail in expression, which promotes induction of EMT process.Therefore,we speculate that miR-23a and miR-410 participate in the EMT process induced Fas signaling.In this study,we will investigate: (1)whether ERK1/2 MAPK enhances miR-23a expression by c-Fos/AP-1 and NFAT4;(2)whether miR-23a and miR-410 can inhibit E-cadherin and Snail respectively;(3)whether miR-23a and miR-410 would serve as a therapeutic target that inhibit Fas-signailing-induced metastasis in CRC.The achievement of this study may provide a new target for CRC diagnosis, therapy and prognosis.