Gut microbiota-mediated hsa_circ_0126925 targets BCAA metabolic enzyme BCAT2 to exacerbate colorectal cancer progression.

IF 4.1 2区 医学 Q2 CELL BIOLOGY
Huihui Yao, Jiancheng Xu, Aina Zhou, Danyang Shen, Qiuchen Dong, Xiaodong Yang, Mengyu Li, Xiuwei Mi, Yang Lu, Runze Zhong, Xinyu Shi, Qingliang Tai, Guoliang Chen, Bo Shi, Liang Sun, Diyuan Zhou, Yizhou Yao, Songbing He
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引用次数: 0

Abstract

Recent evidence indicates that a high-fat diet (HFD) can promote tumor development, especially colorectal cancer (CRC), by influencing the microbiota. Regulatory circular RNAs (circRNAs) play 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 HFD modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein referred to as circ_0126925) in CRC. 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 tumours from limited branched-chain amino acids (BCAAs) interference by improving the metabolism of BCAAs in CRC. Taken together, these data demonstrate that circ_0126925 plays a critical role in promoting the progression of CRC by maintaining BCAA metabolism and provide insight into the functions and crosstalk of circ_0126925 in host-microbe interactions in CRC. 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.

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来源期刊
Molecular Cancer Research
Molecular Cancer Research 医学-细胞生物学
CiteScore
9.90
自引率
0.00%
发文量
280
审稿时长
4-8 weeks
期刊介绍: Molecular Cancer Research publishes articles describing novel basic cancer research discoveries of broad interest to the field. Studies must be of demonstrated significance, and the journal prioritizes analyses performed at the molecular and cellular level that reveal novel mechanistic insight into pathways and processes linked to cancer risk, development, and/or progression. Areas of emphasis include all cancer-associated pathways (including cell-cycle regulation; cell death; chromatin regulation; DNA damage and repair; gene and RNA regulation; genomics; oncogenes and tumor suppressors; signal transduction; and tumor microenvironment), in addition to studies describing new molecular mechanisms and interactions that support cancer phenotypes. For full consideration, primary research submissions must provide significant novel insight into existing pathway functions or address new hypotheses associated with cancer-relevant biologic questions.
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