Inflammatory factor TNFα-induced circDMD mediates R-loop formation to promote tumorigenesis.

Chronic inflammation has been associated with the development of cancer in various anatomical sites. However, the crosstalk between inflammatory factors and circular RNAs (circRNAs) in tumorigenesis is unclear. Here, we revealed that circDMD was upregulated in Tumor necrosis factor alpha-like (TNFα)-induced HeLa cells. circDMD promoted the expression and nuclear translocation of Nuclear factor kappa B subunit (NF-κB) to activate downstream factors. circDMD absorbed miR-4711-5p to increase Lysine demethylase 5 A (KDM5A) expression, which reduced Suppressor of cytokine signaling 1 (SOCS1) to decrease the ubiquitination of Rela proto-oncogene (P65). In addition, circDMD promoted Fms related receptor tyrosine kinase 4 (VEGFR3) expression through the formation of an R-loop in its promoter. circDMD promoted tumor proliferation, metastasis and autophagy by activating the NF-κB pathways in vitro and in tumors derived from HeLa cells in vivo. Taken together, our results indicated that the expression of circDMD is induced by TNFα and contributes to tumorigenesis in cervical cancer (CC), which might help elucidate the regulatory effects of circRNAs on tumorigenesis.