非组蛋白乙酰化修饰在肿瘤转移中起重要作用，但结直肠癌肝转移关键的乙酰化非组蛋白和位点尚属未知。本课题组前期通过蛋白质乙酰化修饰组学等筛选和验证出IDH1 K224位点乙酰化发挥关键作用；异常的细胞外酸性微环境被认为是结直肠癌转移的关键环节，IDH1 K224位点乙酰化影响细胞外酸性微环境。该位点乙酰化可能通过Ago2/miR-9-5p/NHE1通路影响肿瘤酸性微环境调控结直肠癌转移，但分子机制尚不清楚。本课题拟在人结直肠癌组织中探讨IDH1 K224位点乙酰化与Ago2、miR-9-5p、NHE1表达相关性及与预后关系；明确IDH1 K224位点乙酰化调控肿瘤酸性微环境影响结直肠癌转移；探索IDH1 K224位点乙酰化通过Ago2/miR-9-5p通路调控NHE1介导的肿瘤酸性微环境的分子机制。IDH1 K224位点乙酰化影响肿瘤酸性微环境通路研究可能为结直肠肝转移治疗提供新靶点和新策略。

Nonhistone acetylation plays an important part in metastasis process of carcinoma. However, the key acetylated protein and critical acetylated site in CRC metastasis are still obscure. Our preliminary work using acetylated proteomics and site-directed mutation for amino acid showed that K224 of IDH1 was the key acetylated site for liver metastasis of CRC. Abnormal acidic microenvironment was deemed to be a key factor in formation and metastasis of colorectal cancer. IDH1 K224 acetylation might affect the acidic microenvironment around colorectal cancer. IDH1 K224 acetylation might regulate Ago2/miR-9-5p/NHE1 signaling pathway to influence pH-mediated CRC metastasis. However, the underlying mechanisms are still obscure. In this study, we aims to investigate the relationship between IDH1 K224 acetylation and Ago2, or miR-9-5p, or NHE1 expression, as well as the prognosis in CRC tissue samples, to demonsrate IDH1 K224 acetylation indeed influence the acidic microenvironment around tumors, and to explore the mechanism by which IDH1 K224 acetylation regulates Ago2/ miR-9-5p/NHE1 signaling pathway. The research of IDH1 K224 acetylation associated pathways might throw a new light for treatment of liver metastasis in CRC.