Ultraviolet A plays a protective role in ultraviolet B-induced squamous cell carcinoma through c-Fos/XRCC4 axis

For decades, there has been a strong epidemiological association between solar ultraviolet (UV) radiation and skin cancer. UVB and UVA are the major UV bands that can penetrate the atmosphere, playing vital roles in skin carcinogenesis. Our research group previously discovered that a specific dose of UVA can inhibit the increase of activator protein 1 (AP-1) activity caused by UVB. It is unclear whether UVA plays a particular role in UVB-induced skin cancer. Here, we report that UVA was protective in UVB-induced cutaneous squamous cell carcinoma (cSCC) by attenuating UVB-induced DNA damage. DNA repair chip array results showed that the mRNA level of X-ray cross-complementing protein 4 (XRCC4) significantly increased in the UVA/B group compared with the UVB group, and knockdown of XRCC4 partly blocked the protective effect of UVA in UVB-induced DNA damage. AP-1, the predicted transcriptional regulatory factor of XRCC4, exhibited no sensitivity to UVB radiation upon pretreatment with UVA. More importantly, the luciferase reporter assay showed that c-Fos, which is the critical component of AP-1, inhibited the transcription of XRCC4, and mutation of c-Fos (cys154 > serine) partly enhanced this effect and promoted keratinocyte transformation. UVA was protective in UVB-induced cSCC by interacting with the c-Fos/XRCC4 axis.