FADS1-arachidonic Acid Axis Contributes Intestinal Microbial Environment Formation Of Tumor-promoting In Colorectal Cancer

[Objective] In view of the tumor’s own characteristics,the possibility of tumor cells regulating their intestinal microbial environment in colorectal cancer was proposed,and the role of FADS1 in the regulation of peripheral intestinal microbes in colorectal cancer was investigated.The product was found to be arachidonic acid on the intestinal tract.The effects of microbes;revealing that colorectal cancer through the FADS1-arachidonic acid axis induces the formation of a cancer-promoting intestinal microbial environment to promote tumor self-development.[Methods] Tissue microarrays and database information were prepared to verify the role of FADS1 in colorectal cancer.In vitro and in vivo experiments verified the role of FADS1 in CRC.16 S r DNA sequencing to verify the correlation between FADS1 and intestinal microbes in colorectal cancer.Arachidonic acid levels were detected in CRC tissues.The effect of arachidonic acid on intestinal microbes in mice was detected by exogenous arachidonic acid feeding method.The AOM-induced mouse colon adenoma model was further used to verify the changes of arachidonic acid-changing intestinal microbes.[Results] By presenting scientific questions and targeted bioinformatics analysis,we found that FADS1,as an important polyunsaturated fatty acid synthase in human body,is abnormally up-regulated in colorectal cancer and is closely related to the poor prognosis of patients.In vitro cell function experiments showed that knockdown of FADS1 had no significant effect on proliferation and apoptosis of colorectal cancer cells,but in vivo tumor-in-law experiments found that knockdown of FADS1 significantly inhibited the proliferation of colorectal cancer cells,and the results of GSEA analysis showed FADS1 was closely related to the TLR and NOD pathway.16 S r DNA sequencing of colorectal cancer tissues and orthotopic tumor tissues showed that FADS1 and intestinal microbes promoted a series of changes in intestinal flora,among which the number of Escherichia coli,Enterococcus faecalis and Klebsiella pneumoniae in FADS1 high expression group Significantly increased.Further studies found that arachidonic acid in CRC development is also gradually elevated.Further experiments found that FADS1 can regulate the synthesis of arachidonic acid,but can not regulate the release of arachidonic acid,which was significantly affected by intestinal microbial stimulation.Further experiments found that arachidonic acid feeding can change the composition of intestinal microbes in mice,and fecal transplantation experiments have found that these altered intestinal microbes can promote the development of colon adenomas.[Conclusion] The abnormally high expression of FADS1 is closely related to the development of colorectal cancer.FADS1-arachidonic acid axis induced a cancer-promoting intestinal microbial environment,which promoted CRC development.