具核梭杆菌介导长链非编码RNA uc.173/miR-29b调节自噬蛋白ATG12促进结肠癌进展的分子机制研究

肠道菌群与结肠癌发生发展的相关性研究引起普遍关注。本课题组前期通过动物模型明确了具核梭杆菌促进结肠癌发生发展，对具核梭杆菌感染小鼠肠粘膜进行RNA-seq高通量测序，发现肠粘膜自噬蛋白ATG12上调，WB及免疫荧光结果也证实了具核梭杆菌感染可激活ATG12；此外长链非编码RNA uc.173表达增高。经生物信息学预测及实验验证，uc.173可通过结合并抑制miR29b从而上调ATG12，为进一步研究具核梭杆菌在转录后水平促进结肠癌发生发展的分子机制提供了有力的证据和线索。本课题将围绕“具核梭杆菌在转录后水平介导自噬蛋白促进结肠癌发生发展”的科学问题，以结肠癌细胞、小鼠及Organoid类器官培养物为载体，深入研究具核梭杆菌感染介导uc.173/miR 29b调节自噬蛋白ATG12促进结肠癌发展的分子机制，为寻找新的基于肠道菌群的结肠癌干预和治疗靶点提供依据。

Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer, which brings great attentions widely. In our previous study, to address its tumor genesis, we selected F.nucleatum ATCC 25586 stain, which was found to be related with colorectal cancer. With the help of RNA-seq technique, we undertook a critical dataset of differential genes after Fusobacterium nucleatum infection with a focus on ATG12, which was up-regulated by Fusobacterium nucleatum. As the key pathway to reveal the oncogenic mechanism, we checked the ATG12 protein level in vitro after Fusobacterium nucleatum infection. The increasing level of ATG12 indicated that the Fusobacterium nucleatum may have an impact on tumor progression by up-regulated ATG12. Based on these findings, we will delve into recent insights and future directions for fusobacterial mechanism research, including the increased ATG12 regulated by long-noncoding RNA uc.173 and miR-29b axis at in vitro, in vivo and ex-vivo levels. Our understanding of its mechanistic role in promoting colorectal cancer may lay foundation for developing diagnostics and therapeutics for Fusobacterium nucleatum.