Lang Yanhong, Zhong Chengrui, Guo Lingling, Liu Zhijie, Zuo Dinglan, Chen Xi, Ding Liuyan, Huang Bijun, Li Binkui, Yuan Yunfei, Niu Yi, Qiu Jiliang, Qian Chaonan
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China.
Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P.R. China.
iScience. 2024 Jun 6;27(7):110205. doi: 10.1016/j.isci.2024.110205. eCollection 2024 Jul 19.
Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apc mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway . Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.
单酰甘油酰基转移酶-2（MOGAT2）在三酰甘油的重新合成中编码MOGAT酶，并能预防代谢紊乱。然而，其在结直肠癌（CRC）进展中的具体作用仍未得到充分了解。我们的研究表明，在Apc小鼠中敲除Mogat2会加速肠道肿瘤的生长和进展，这表明Mogat2在CRC中发挥着肿瘤抑制作用。从机制上讲，Mogat2的缺失导致肠道微生物群发生显著改变，而粪便微生物群移植（FMT）实验表明，Mogat2缺失小鼠的肠道微生物群促进了肿瘤生长。此外，我们确定Mogat2是一种功能性调节因子，通过抑制NF-κB信号通路来抑制CRC细胞增殖和肿瘤生长。总的来说，这些结果为Mogat2的双重保护作用提供了新的见解，即在结直肠癌中抑制NF-κB通路和维持肠道微生物群稳态，这可能有助于开发针对CRC的新型癌症治疗方法。
