Monoacylglycerol acyltransferase-2 inhibits colorectal carcinogenesis in APCmin+/- mice

单酰基甘油酰基转移酶-2 抑制 APCmin+/- 小鼠的结肠直肠癌发生

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作者:Yanhong Lang, Chengrui Zhong, Lingling Guo, Zhijie Liu, Dinglan Zuo, Xi Chen, Liuyan Ding, Bijun Huang, Binkui Li, Yunfei Yuan, Yi Niu, Jiliang Qiu, Chaonan Qian

Abstract

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 Apcmin/+ 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 in vivo. 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.

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