结直肠腺瘤(CRA)尤其是进展性腺瘤(ACRA)是结直肠癌(CRC)的癌前病变，80%以上的CRC系由CRA通过ACRA进展而来，因此阻断CRA-ACRA途径是预防CRC的关键。MiR-194可抑制结肠肿瘤细胞增殖。我们前期采用microRNA高通量芯片结合回顾性临床验证，发现miR-194在ACRA中的表达较正常者显著降低，腺瘤切除后再发者较未再发者显著降低，可作为腺瘤进展过程的预警标志。MiR-194可通过调控靶基因AKT2的表达发挥作用，但确切机制尚未明了。本研究欲采用细胞实验，探讨miR-194在CRA发生发展中的作用和机制，阐明 ①miR-194是否通过调控靶基因AKT2而在CRA的发生发展中起作用；② miR-194受EZH2的组蛋白甲基化修饰后影响AKT2的表达继而促进CRA发生发展的机制。有助于更好地随访和监控CRA，并为早期防治CRC提供治疗靶点奠定理论基础。

Colorectal adenomas (CRA), especially advanced colorectal adenomas (ACRA) are the accepted precancerous lesions of colorectal cancer (CRC). More than eighty percent of CRC are developed by CRA through ACRA, so the key point for CRC prevention is to block the CRA-ACRA pathway. MiR-194 can inhibit the proliferation of colorectal cancer cells. In our previous study, we found that the expression of miR-194 is gradually downregulated in the normal colorectal tissue, ACRA with no adenoma recurrence and ACRA with adenoma recurrence, based on miRNA microarray analysis and retrospective cohort validation. MiR-194 is a potential biomarker in the progression of CRA. MiR-194 may play a crucial role in the progression of CRA through targeting AKT2, but the more elucidated mechanism remained to be revealed. Therefore, in this study we will focus on the effect and mechanism by which miR-194 mediates in the progression of CRA. Based on our preliminary data we will 1.demonstrate the effect of miR-194 in the progression of CRA via modulating target gene AKT2; 2.evaluate the mechanism by which miR-194 induces alteration of AKT2 gene expression in response to miR-194 histone methylation with EZH2 in CRA progress in vitro. In a word, our research may provide theoretical basis for individualized surveillance and for potential therapeutic target.