Loss of retinoic acid receptor-related receptor alpha (Rorα) promotes the progression of UV-induced cSCC

Cutaneous squamous cell carcinoma (cSCC) is prevalent in the world, accounting for a huge part of non-melanoma skin cancer. Most cSCCs are associated with a distinct pre-cancerous lesion, the actinic keratosis (AK). However, the progression trajectory from normal skin to AK and cSCC has not been fully demonstrated yet. To identify genes involved in this progression trajectory and possible therapeutic targets for cSCC, here we constructed a UV-induced cSCC mouse model covering the progression from normal skin to AK to cSCC, which mimicked the solar UV radiation perfectly using the solar-like ratio of UVA and UVB, firstly. Then, transcriptome analysis and a series of bioinformatics analyses and cell experiments proved that Ror alpha is a key transcript factor during cSCC progression. Ror alpha could downregulate the expressions of S100a9 and Sprr2f in cSCC cells, which can inhibit the proliferation and migration in cSCC cells, but not the normal keratinocyte. Finally, further animal experiments confirmed the inhibitory effect of cSCC growth by Ror alpha in vivo. Our findings showed that Ror alpha would serve as a potential novel target for cSCC, which will facilitate the treatment of cSCC in the future.

Automated summary

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, often associated with actinic keratosis (AK). By constructing a UV-induced cSCC mouse model, researchers identified Ror alpha as a key transcription factor in cSCC progression, suggesting it as a potential novel target for cSCC treatment in the future.