KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF.

中文翻译：

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KRAS 突变通过调节 miRNA3655/SURF6/IRF7/IFNβ 轴促进结直肠癌中产肠毒素脆弱拟杆菌的瘤内定植。


KRAS 突变与结直肠癌 （CRC） 的不良预后相关。尽管肠道菌群与 CRC 之间的关联已被广泛记录，但尚不清楚 KRAS 突变是否可以调节肠道菌群。宏基因组学已经确定了由于 KRAS 突变导致 CRC 肠道菌群多样性的变化。具体来说，KRAS 突变与拟杆菌的丰度呈正相关。了解如何调节拟杆菌体内的典型致癌细菌，如产肠毒素脆弱拟杆菌 （ETBF），以提高肿瘤的治疗效果是研究的重点。从机制上讲，我们发现 miR3655 的减少对于 KRAS 突变促进的 CRC 增殖和 ETBF 的丰度是必不可少的。miR3655 靶向 SURF6 以抑制其转录。进一步的转录组测序显示，SURF6 通过抑制 IRF7 的核转位和转录水平促进 ETBF 在 CRC 中的瘤内定植，从而影响 IFNβ 启动子的激活。调节 miR3655 和 SURF6 可促进 CRC 中 IFNβ 的分泌，直接杀死 ETBF。这些数据表明，KRAS 突变通过 miR3655/SURF6/IRF7/IFNβ 轴影响 ETBF 在 CRC 中的瘤内定植。这为治疗与 KRAS 突变或高水平的 ETBF 相关的 CRC 提供了新的潜在策略。