结直肠癌严重危害人民生命健康。我们前期发现：功能微小RNA文库筛选到miR-148a抑制结直肠癌生长；miR-148a在结直肠癌表达下调与病人临床预后相关；P65招募DNMT3A升高miR-148a启动子甲基化而抑制其表达；miR-148a在肠上皮和免疫组织广泛表达；利用同源重组技术构建了miR-148a敲除小鼠，它的缺失增加DSS诱发结肠炎严重性和加剧AOM/DSS诱导结直肠癌变，并改变肠道菌群平衡。本项目应用现代实验技术进一步研究miR-148a缺失是否促进自发性结直肠和小肠肿瘤的形成及在结直肠癌变中它调控的靶基因及信号通路，它的缺失怎样改变肠道菌群平衡而调节结直肠癌变，并行防治研究。这将揭示miR-148a在调控肠道菌群平衡和结直肠癌变中的作用分子机理，为防治这类疾病提供坚实的理论基础和新策略。

Colorectal cancer seriously does harm to people's lives and health. Previously we have found that: miR-148a was identified to significantly inhibit colorectal cancer growth using high-content functional miRNA library screening; miR-148a downregulation correlated with human colorectal cancer patient clinical stages and survival; miR-148a promoter was highly methylated by a complex comprised of P65 and DNA methyltransferase 3 alpha (DNMT3A) in human colorectal cancer; miR-148a is widely expressed in the digestive tract epithelium and immune tissues; the miR-148a knockout mice were successfully constructed by homologous recombination; miR-148a-deficient mice were more susceptible to colitis and colitis-associated tumorigenesis; Cohousing experiments revealed that miR-148a deficiency altered gut microbiota balance. This project continues to further study whether miR-148a deficiency promotes the development of spontaneous colorectal and small intestine cancer and the targets and signal pathways regulated by miR-148a; to further study miR-148a deficiency altering gut microbiota balance and exacerbating colitis-associated tumorigenesis using series of modern experimental technology. It will clarify its roles in the prevention and treatment colorectal cancer through targeted intervention. This will reveal the molecular mechanism of miR-148a deficiency altering gut microbiota balance and exacerbating colorectal tumorigenesis, which will provide theoretical basis and new strategies for the prevention and treatment of these diseases.