Huang Yi-Wen, Lin Chien-Wei, Pan Pan, Echeveste Carla Elena, Dong Athena, Oshima Kiyoko, Yearsley Martha, Yu Jianhua, Wang Li-Shu
Department of Obstetrics & Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.
Division of Biostatistics, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
J Cancer Prev. 2021 Mar 30;26(1):32-40. doi: 10.15430/JCP.2021.26.1.32.
Free fatty acid receptor 2 () has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model ( ). deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, , and - mice. The relative abundance of and was significantly increased in the - mice compared to the mice. In addition, knocking-down in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.
游离脂肪酸受体2（）已被报道在结肠癌发生发展过程中作为一种肿瘤抑制因子。当前研究在一种结直肠癌小鼠模型（）中探究了信号对能量代谢和肠道微生物群谱的影响。缺乏会促进结肠息肉发展，并增强脂肪酸氧化和胆汁酸代谢。肠道微生物组测序分析显示野生型、和小鼠之间存在明显聚类。与小鼠相比，小鼠中及的相对丰度显著增加。此外，在人结肠癌细胞系（SW480和HT29）中敲低会导致脂肪酸氧化中几种关键酶的表达增加，如肉碱棕榈酰转移酶2、酰基辅酶A脱氢酶、长链酰基辅酶A脱氢酶、C-2至C-3短链以及羟酰基辅酶A脱氢酶/3-酮酰基辅酶A硫解酶/烯酰基辅酶A水合酶α亚基。总体而言，这些结果表明缺乏会显著改变脂肪酸代谢产物和肠道微生物群谱，这可能促进结直肠癌的发展。
