Integrative Genomic and Functional Approaches Identify FUOM as a Key Driver and Therapeutic Target in Cervical Cancer
ABSTRACT 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 understoo...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.70306 |
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| Summary: | ABSTRACT 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. |
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| ISSN: | 2573-8348 |