Recently, a team from the Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, discovered that the miR-149-3 (microRNA miR-149-3p ) Reduces, and promotes Th17 (T helper cell 17) differentiation. ETBF down-regulates miR-149-3p and further promotes the variable cleavage of RNA (ribonucleic acid) of KAT2A (histone acetylase) mediated by PHF5A (key factor of protein cleavage complex), and finally induces the occurrence of colorectal cancer. The research results were published online in "Gastroenterology".
Bacillus fragilis toxin (BFT) secreted by ETBF infection can cause diarrhea in domestic animals and humans, and it can also live in the intestines of some people without symptoms. The main pathogenic factor of ETBF is that it can secrete BFT. In recent years, ETBF is closely related to the occurrence of inflammatory bowel disease and colitis related colorectal cancer and colorectal cancer. However, the mechanism by which ETBF induces intestinal inflammation and tumorigenesis remains unclear.
In this study, the researchers found that miR-149-3p was reduced in exosomes produced after ETBF treatment of colorectal cancer cells, which promoted the differentiation of Th17 cells. ETBF down-regulates miR-149-3p and further promotes PHF5A-mediated KAT2A RNA variable cleavage, and ultimately induces the occurrence of colorectal cancer. In addition, it was found in clinical sample verification that the content of miR-149-3p encapsulated by exosomes was significantly reduced in colorectal cancer and active enteritis patients. MiR-149-3p has the potential to become a biomarker for predicting the transformation of enteritis into cancer and the progress of enteritis activities. Targeting the ETBF/miR-149-3p pathway can be used as a potential medical treatment to treat patients with ETBF-rich enteritis and colorectal cancer in the intestine.
Researchers also found that ETBF promotes the proliferation of colorectal cancer cells by down-regulating miR-149-3p in vitro and in vivo. The down-regulation of miR-149-3p by ETBF depends on the methylation of m6A mediated by METTL14 (RNA methyltransferase 14).After ETBF treats colorectal cancer cells, the target gene of miR-149-3p—PHF5A activates SOD2 by regulating the variable splicing of KAT2A mRNA. miR-149-3p can be encapsulated in exosomes and released and mediate cell-to-cell communication by regulating Th17 cell differentiation. The content of miR-149-3p in plasma exosomes gradually decreases in healthy controls, inflammatory bowel disease and colorectal cancer patients. The presence of miR-149-3p in plasma exosomes is negatively correlated with the abundance of ETBF in the intestine of patients with inflammatory bowel disease and colorectal cancer.
This basic study combined with clinical validation has established a new mechanism for ETBF to promote enteritis and colorectal cancer, and provides strong evidence that ETBF and miR-149-3p encapsulated in exosomes can act as inflammatory bowel disease and colorectal cancer Patients' potential prognostic evaluation indicators and treatment targets.
The corresponding authors of the paper are Renji Hospital Gastroenterology Researcher Hong Jie and Chen Haoyan, Renji Hospital Gastroenterology Doctoral Candidate Cao Yingying, Wang Zhenhua Associate Chief Physician, Doctoral Candidate Yan Yuqing, Gastrointestinal Surgery Doctor Ji Linhua, Guangzhou City No. Professor He Jie from the Department of Gastroenterology of the First People's Hospital is the co-first author. This research was supported by the director of Fang Jingyuan of the Department of Gastroenterology and a number of grants from the National Natural Science Foundation of China.
Author: Shanghai Radio reporter Lu Chunlu
Editor: Zuo Yu
Editor in charge: Zhu Ying
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