Identification of RCC2 as a Risk Gene Associated With Basal Cell Carcinoma and Experimental Validation

Area of Science:

• Genetics and Genomics
• Dermatology
• Cancer Biology

Background:

• Basal cell carcinoma (BCC) prevalence is rising globally, with known genetic links but undiscovered disease-causing genes.
• The sonic hedgehog (SHH) pathway is a key driver, but novel targets are needed alongside existing therapies like vismodegib.

Purpose of the Study:

• To identify novel genetic factors associated with basal cell carcinoma (BCC) risk.
• To investigate the role of identified genes in BCC pathogenesis and explore potential therapeutic strategies.

Main Methods:

• Utilized Mendelian Randomization (MR) with multi-omics data (eQTL, mQTL, pQTL) to identify BCC risk genes.
• Verified gene expression using transcriptome analysis (GEO database) and single-cell RNA sequencing.
• Performed in vitro experiments to assess the effect of gene silencing on A431 cell proliferation.

Main Results:

• Identified six CpG sites linked to BCC risk, with the RCC2 gene being a key factor.
• Confirmed specific expression of RCC2 in BCC cohorts via single-cell transcriptome analysis.
• In vitro knockdown of RCC2 significantly inhibited A431 cell proliferation.

Conclusions:

• Discovered RCC2 as a novel gene associated with basal cell carcinoma (BCC) risk through MR-based bioinformatics.
• Demonstrated that inhibiting RCC2 suppresses BCC cell proliferation in vitro.
• Findings suggest RCC2 as a potential new target for BCC-targeted therapies.