TY - JOUR T1 - <em>F. nucleatum</em> targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer JF - Gut JO - Gut SP - 2123 LP - 2137 DO - 10.1136/gutjnl-2020-322780 VL - 70 IS - 11 AU - Jie Hong AU - Fangfang Guo AU - Shi-Yuan Lu AU - Chaoqin Shen AU - Dan Ma AU - Xinyu Zhang AU - Yile Xie AU - Tingting Yan AU - TaChung Yu AU - Tiantian Sun AU - Yun Qian AU - Ming Zhong AU - Jinxian Chen AU - Yanshen Peng AU - Cheng Wang AU - Xiang Zhou AU - Jianjun Liu AU - Qiang Liu AU - Xiong Ma AU - Ying-Xuan Chen AU - Haoyan Chen AU - Jing-Yuan Fang Y1 - 2021/11/01 UR - http://gut.bmj.com/content/70/11/2123.abstract N2 - Objective Microbiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.Design 18F-FDG (18F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in Fusobacterium (F.) nucleatum-induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.Results We have found F. nucleatum abundance correlated with high glucose metabolism in patients with CRC. Furthermore, F. nucleatum supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, F. nucleatum activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.Conclusion F. nucleatum and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated F. nucleatum.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All data and source associated with this study are available from the corresponding author on reasonable request. ER -