Circular RNA circ_0004470 accelerates the occurrence of lung cancer by promoting DNA damage and cell cycle arrest.

Defects in the DNA damage response are associated with tumorigenesis, and circular RNAs (circRNAs) can also affect the occurrence and progression of cancer by regulating gene expression. However, the relationship between DNA damage in lung cancer and circRNAs remains unexplored. In this study, circ_0004470 was significantly upregulated in various lung cancer cells (H446, A549, H1299) as well as in carcinogenic animal models and clinical lung cancer samples. Circ_0004470 promoted DNA damage and cell cycle S phase arrest in human pulmonary bronchial epithelial cells, inhibited DNA repair, and accelerated malignant transformation in response to continuous DNA damage-inducing stimulation. Circ_0004470 inhibited DNA repair and cell cycle progression by binding specifically to the nucleotide excision repair complex Xeroderma pigmentosum group C-complementing protein and damage-specific DNA binding protein 1, thus interacting with the DNA damage response process and accelerating the accumulation of DNA damage. These findings suggest that circRNAs are involved in regulating genetic damage-associated lung cancer and provide insight into the mechanism by which circ_0004470 affects the DNA damage response during carcinogenesis.