癌变
结直肠癌
生物
癌症研究
染色质免疫沉淀
癌症
核梭杆菌
遗传学
基因表达
基因
发起人
细菌
牙龈卟啉单胞菌
作者
Jie Hong,Fangfang Guo,Shiyuan Lu,Chaoqin Shen,Dan Ma,Xinyu Zhang,Yile Xie,Tingting Yan,TaChung Yu,Tiantian Sun,Yun Qian,Ming Zhong,Jinxian Chen,Yanshen Peng,Cheng Wang,Xiang Zhou,Jing Liu,Qiang Liu,Xiong Ma,Yingxuan Chen,Haoyan Chen,Jing‐Yuan Fang
出处
期刊:Gut
[BMJ]
日期:2020-12-14
卷期号:70 (11): 2123-2137
被引量:169
标识
DOI:10.1136/gutjnl-2020-322780
摘要
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 18 F-FDG ( 18 F-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 .
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