MiR-581-PRDX1信号轴通过调控上皮-间质转化抑制结直肠癌转移的分子机制研究

Epithelial-mesenchymal transition (EMT) is closely correlated to human colorectal carcinoma (CRC) metastasis, but its molecular mechanism still remains unclear. In previous study, we have confirmed that peroxiredoxin 1 (PRDX1) is highly expressed in CRC tissues, and promotes cancer metastasis through regulating EMT. Combined with the tissue chip screening and bioinformatics analysis, we have screened a novel PRDX1 interacting molecule—miR-581, and found that the expression of miR-581 in metastatic tissues is significant lower than those from non-metastatic tissues. Here, we propose that down-regulation of miR-581 leads to the PRDX1 increasing in CRC tissues, and the miR-581/PRDX1 axis may contribute to CRC metastasis..This project plans to investigate the interaction between miR-581 and PRDX1 on the cell level by luciferase reporter system. Morevoer, we further elucidate the effects of miR-581 targeting PRDX1 on EMT and metastasis, and explore the underlying molecular mechanisms through which miR-581- PRDX1 signaling axis regulates EMT and therefore to inhibit CRC metastasis by using operation specimens and tumor bearing mice models. The study will aim to elaborate the potenrial role of miR-581 in CRC metastasis, develop a new miRNA pathway in regulation of CRC metastasis, and to provide a solid experimental basis for target regulating strategy on colorectal cancer treatment.

上皮-间质转化（EMT）与结直肠癌（CRC）转移密切相关，其分子调控机制仍未阐明。前期研究已证实过氧化还原酶1（PRDX1）在CRC中高表达，并可调控EMT促进CRC转移。通过进一步研究，我们筛选到一个新的PRDX1互作分子—miR-581，且发现miR-581在有转移CRC组织中的表达水平明显低于无转移癌组织，因而推测：CRC中高表达PRDX1与miR-581失调有关；miR-581的下调表达可能是导致CRC转移的重要因素。本项目拟通过荧光素酶报告系统等从细胞水平确定miR-581和PRDX1二者间作用关系；结合临床组织标本和动物模型，明确miR-581靶向PRDX1后对EMT表型及转移的影响，探讨miR-581-PRDX1信号轴调控EMT抑制CRC转移的分子机制，旨在阐释miR-581在CRC转移中发挥的重要功能，以期寻求一条CRC转移调控的miRNA新通路，为其靶向策略提供依据。

上皮-间质转化（EMT）与结直肠癌（CRC）转移密切相关，其分子调控机制仍未阐明。前期研究已证实过氧化还原酶1（PRDX1）在CRC中高表达，并可调控EMT促进CRC转移。通过进一步研究，我们筛选到一个新的PRDX1互作分子—miR-581，且发现miR-581在有转移CRC组织中的表达水平明显低于无转移癌组织，因而推测：结直肠癌中高表达PRDX1与miR-581失调有关；miR-581的下调表达可能是导致CRC转移的重要因素。本项目拟通过荧光素酶报告系统等从细胞水平确定miR-581和PRDX1二者间作用关系；结合临床组织标本和动物模型，明确miR-581靶向PRDX1后对EMT表型及转移的影响，探讨miR-581-PRDX1信号轴调控EMT抑制CRC转移的分子机制，旨在阐释miR-581在CRC转移中发挥的重要功能，以期寻求一条CRC转移调控的miRNA新通路，为其靶向策略提供依据。