F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer
F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer
复制标题
F. nucleatum 靶向 lncRNA ENO1-IT1 以促进结直肠癌中的糖酵解和肿瘤发生。
DOI：
10.1136/gutjnl-2020-322780
复制
发表时间：
2021-11-01
期刊：
影响因子：
24.5
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Hong, Jie;Guo, Fangfang;Fang, Jing-Yuan
目的微生物群紊乱促进慢性炎症和癌变。高糖酵解与结直肠癌（CRC）患者预后不良相关。然而，在结直肠癌中，肠道微生物群与葡萄糖代谢之间的潜在相关性尚不清楚。设计对33例结直肠癌患者进行18F-FDG （18f -氟脱氧葡萄糖）PET（正电子发射断层扫描）/CT图像扫描数据和微生物群PCR分析，以测定代谢改变与微生物群紊乱之间的相关性。通过建立多种结直肠癌模型、代谢分析和海马实验，研究长链非编码RNA （lncRNA）烯醇化酶-内含子转录物1 （ENO1-IT1）在梭杆菌（F.）核核诱导的葡萄糖代谢和结直肠癌发生中的作用。通过RNA免疫沉淀和染色质免疫沉淀测序来鉴定lncRNA ENO1-IT1的潜在靶点。结果我们发现核梭菌丰度与结直肠癌患者的高糖代谢相关。此外，核梭菌通过增加结直肠癌细胞葡萄糖代谢来支持癌变。从机制上讲，F. nucleatum通过上调转录因子SP1对lncRNA ENO1-IT1启动子区的结合效率来激活lncRNA ENO1-IT1的转录。升高的ENO1- it作为KAT7组蛋白乙酰转移酶的引导模块，指定其靶基因（包括ENO1）上的组蛋白修饰模式，从而改变CRC的生物学功能。结论核梭菌和糖代谢与结直肠癌的发生有机制、生物学和临床联系。以ENO1通路为靶点治疗结直肠癌具核梭菌升高患者可能有意义。
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.