Abstract
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 Rorα is a key transcript factor during cSCC progression. Rorα 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 Rorα in vivo. Our findings showed that Rorα would serve as a potential novel target for cSCC, which will facilitate the treatment of cSCC in the future.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calgranulin B / genetics
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Calgranulin B / metabolism
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Carcinoma, Squamous Cell / etiology
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Cornified Envelope Proline-Rich Proteins / genetics
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Cornified Envelope Proline-Rich Proteins / metabolism
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Disease Models, Animal
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Disease Progression
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Keratosis, Actinic / etiology
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Keratosis, Actinic / genetics
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Keratosis, Actinic / metabolism*
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Keratosis, Actinic / pathology
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Mice
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Mice, Hairless
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Neoplasm Invasiveness
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Neoplasms, Radiation-Induced / etiology
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Neoplasms, Radiation-Induced / genetics
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Neoplasms, Radiation-Induced / metabolism*
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Neoplasms, Radiation-Induced / pathology
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Nuclear Receptor Subfamily 1, Group F, Member 1 / deficiency*
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Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
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Octamer Transcription Factors / genetics
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Octamer Transcription Factors / metabolism
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Skin Neoplasms / etiology
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Skin Neoplasms / genetics
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Skin Neoplasms / metabolism*
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Skin Neoplasms / pathology
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Transcriptome
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Ultraviolet Rays
Substances
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Calgranulin B
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Cornified Envelope Proline-Rich Proteins
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Nuclear Receptor Subfamily 1, Group F, Member 1
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Octamer Transcription Factors
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POU2F3 protein, human
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Pou2f3 protein, mouse
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RORA protein, human
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Rora protein, mouse
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S100A9 protein, human
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S100A9 protein, mouse
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SPRR2F protein, human
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Sprr2f protein, mouse