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Series GSE251675

Query DataSets for GSE251675

Status

Public on Jan 16, 2024

Title

Differentially expressed genes induced by UVB stimulation between the P2ry6+/+ and P2ry6-/- mice

Organism

Mus musculus

Experiment type

Expression profiling by array

Summary

Considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we find that P2ry6 deletion exhibits marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, P2ry6 knockout promotes mouse skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, can inhibit UVB-induced skin damage. Furthermore, UVB irradiation can significantly upregulate P2RY6 expression in mouse and human skin cells. These results indicate that P2RY6 plays a crucial protective role in resisting UVB-induced skin damage and carcinogenesis. At the molecular level, P2RY6 deletion inhibits ubiquitination and expression of XPC after UVB irradiation in keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). P2RY6 deletion also activates PI3K/AKT signaling pathway in vitro and in vivo. The CPD accumulation and inflammatory responses enhanced by P2RY6 deletion are reversed by an AKT inhibitor. These findings suggest that P2RY6 acts as a tumor suppressor in UVB-induced skin cancer by regulating PI3K/AKT signaling pathway.

Overall design

Twenty pairs of two-month-old P2ry6+/+ and P2ry6-/- mice were housed in SPF conditions with free access to food and tap water. In order to induce epidermal hyperplasia, the dorsal skins of mice were shaved, followed by UVB irradiation at a dose of 180mJ/cm2, administered three times per week for two consecutive weeks. In order to induce skin tumor formation, mice were irradiated with 180mJ/cm2 UVB for initial ten weeks, increasing 10mJ/cm2 every week to the dose of 300mJ/cm2 at week 22 and keeping it until to week 40. The tumors on the backs of the mice were counted weekly after becoming visible. The incidence of mouse tumors and multiplicity of tumors were also calculated.

Contributor(s)

Peng X, Yongyan D

Citation missing

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Submission date

Dec 20, 2023

Last update date

Jan 16, 2024

Contact name

xu peng

E-mail(s)

xunuoqing0530@126.com