V.parvula regulates JAK2-STAT3 to promote colorectal cancer

Abstract Background: The dysregulation of the gut microbiota is associated with the occurrence and development of colorectal cancer. Several clinical studies have indicated that the abundance of Veillonella parvula in the intestines of colorectal cancer patients is higher than that in the normal population. The aim of this study is to explore the mechanisms through which Veillonella parvula promotes colorectal cancer. Methods: Establish a colorectal cancer mouse model to assess the tumor-promoting effect of Veillonella parvula. Utilize RNA-seq, Western blot, and other techniques to examine the expression of relevant molecules. Furthermore, employ two human colorectal cancer cell lines in vitro to validate the relationship between complement C3 and the JAK2-STAT3 signaling pathway. Results: In comparison to the control group, mice administered with Veillonella parvula exhibited an increased number and size of intestinal tumors. Furthermore, a significant enhancement in the expression of C3 and C3a receptor proteins was noted in the colorectal tissues of mice treated with Veillonella parvula. The results from in vitro experiments indicated that the addition of exogenous C3 in the culture of colorectal cancer cells activated the JAK2 - STAT3 signaling pathway. The activation was attenuated upon the introduction of the JAK2 inhibitor AG490. Conclusion: Veillonella parvula enhances complement C3 expression in colonic tissue, activating the JAK2-STAT3 signaling pathway and promoting colorectal cancer development.