miRNA在双酚A诱导结直肠癌上皮间质化中的作用及机制

Bisphenol A (BPA), a food contaminant with endocrine disruptor activity, is a widespread environmental pollutant. Since the gut is in direct contact with orally absorbed BPA, effects on occurrence and development of colorectal cancer have aroused people’s concern. Colorectal cancer (CRC) is the 3rd most common malignancy worldwide. In china, colorectal cancer annual incidence rates are rapidly increasing in last decade. Our previous work at the first time showed that exposure to BPA can significantly promote migration and invasion ability via trigger the epithelial- mesenchymal transition (EMT) of colorectal cancer cells. Further, we found the effect of BPA exposure on alterations in miR-17 expression was associated with migration and invasion. Our results suggest that miRNA expression modulation may be critical mediators of BPA-induced EMT of colorectal cancer. On this basis, this project intends to research the mechanism of miRNA in mediating BPA-induced EMT of colorectal cancer by using a series of cancer phamarcological, molecular biological methods and technologies. This study will serves to demonstrate the utility of miRNA expression profiles in bettering our understanding of the action of environmental toxicants. The successful completion of this project will elucidate the role of miRNA in BPA-induced EMT of colorectal cancer. It shows the great value to inspire us for developing the novel anti-cancer strategy and create new opportunity for cancer prevention and therapy.

双酚A（BPA）是广泛存在的环境污染物，环境内分泌干扰物的一种，主要通过食物吸收的方式进入体内。胃肠作为食物消化吸收的器官而直接暴露于BPA中，因此BPA对结直肠癌的影响值得我们的关注。结直肠癌是近几年来发病率不断上升且严重影响人类健康的恶性肿瘤，前期研究首次发现BPA暴露能够显著改变结直肠癌细胞的形态，使之发生上皮-间质化转变（EMT），从而促进结直肠癌细胞的侵袭转移能力。进一步研究发现BPA诱导下的结直肠癌细胞EMT过程与miR-17的上调密切相关。由此我们推测miRNA可能介导了BPA对结直肠癌细胞EMT的促进作用。本项目拟在前期研究基础上，利用miRNA芯片技术从miRNA的角度系统、全面地揭示BPA对结直肠癌EMT促进作用的机制，阐明其过程中起关键调节作用的miRNA，以期为结直肠癌的预防和治疗提供坚实的理论依据。同时，通过该研究拓展人们对结直肠癌发生发展机制的视野。