Integrative Genomic and Functional Approaches Identify FUOM as a Key Driver and Therapeutic Target in Cervical Cancer

Background

Cervical cancer remains a global public health challenge, particularly in regions with limited access to screening and vaccination. While high-risk HPV infection is the primary cause, the genetic and molecular mechanisms driving cervical cancer progression are not fully understood.

Objective

This study integrates Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to identify causal eQTL-related genes and explore their roles in tumorigenesis. Functional experiments were conducted to validate key findings.

Methods

MR analysis identified eQTL-related genes with significant causal associations with cervical cancer. Functional enrichment and Gene Set Variation Analysis (GSVA) revealed their involvement in key pathways. scRNA-seq explored cell-specific expression patterns and immune cell infiltration in the tumor microenvironment (TME). In vitro experiments, including qRT-PCR, siRNA knockdown, migration, proliferation, and colony formation assays, validated the biological roles of pivotal genes.

Results

A total of 307 eQTL-related genes were identified, enriched in pathways such as Th17 cell differentiation, TNF, and IL-17 signaling. scRNA-seq revealed cell-specific expression of key genes, including FUOM, which was elevated in cervical cancer cells. FUOM knockdown significantly reduced cell proliferation (by 37%, p < 0.001), migration (by 43%, p < 0.001), and colony formation (by 62%, p < 0.001). Regulatory analysis identified miRNAs as upstream modulators of these genes.

Conclusion

This study identifies FUOM as a novel driver gene in cervical cancer progression and highlights its role in tumorigenesis and immune modulation. These findings provide insights into potential biomarkers and therapeutic targets, offering a foundation for personalized treatment strategies.