Funding
Suzhou Gusu Medical Youth Talent
National Natural Science Foundation of China (NSFC)
New Pharmaceutics and Medical Apparatuses Project of Suzhou City
Provincial - level Talent Program for National Center of Technology Innovation for Biopharmaceutics
Basic Reseach Pilot Project of Suzhou City of China
Project of Suzhou Top-Notch Talent Groups
Interdiciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow University
ARTICLE ABSTRACT
Recent evidence indicates that a high-fat diet can promote tumor development, especially colorectal cancer, by influencing the microbiota. Regulatory circular RNA (circRNA) plays an important role in modulating host–microbe interactions; however, the specific mechanisms by which circRNAs influence cancer progression by regulating these interactions remain unclear. Here, we report that consumption of a high-fat diet modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein, referred to as circ_0126925) in colorectal cancer. Acting as a scaffold, circ_0126925 hinders the recruitment of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) to branched-chain amino acid transaminase 2 (BCAT2), leading to reduced degradation of BCAT2. This reduction in targeted degradation of BCAT2 can protect tumors from limited branched-chain amino acid (BCAA) interference by improving the metabolism of BCAAs in colorectal cancer. Taken together, these data demonstrate that circ_0126925 plays a critical role in promoting the progression of colorectal cancer by maintaining BCAA metabolism and provide insight into the functions and crosstalk of circ_0126925 in host–microbe interactions in colorectal cancer.Implications: This study preliminarily confirms that circRNAs do indeed respond to microbiota/microbial metabolites, providing further evidence for the potential development of circRNAs as diagnostic tools and/or therapeutic agents to alleviate microbiome-related pathology in humans.
