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

**Authors:** Wenzhi Jiao, Shanshan Liu, Jianwei Shi, Minmin Yu

PMC · DOI: 10.1002/cnr2.70306 · Cancer Reports · 2025-08-16

## TL;DR

This study identifies the gene FUOM as a key driver in cervical cancer and shows that targeting it could reduce cancer cell growth and spread.

## Contribution

The study introduces FUOM as a novel therapeutic target in cervical cancer using integrative genomic and functional approaches.

## Key findings

- FUOM knockdown reduced cell proliferation by 37%, migration by 43%, and colony formation by 62%.
- eQTL-related genes were enriched in pathways like Th17 cell differentiation and IL-17 signaling.
- scRNA-seq revealed cell-specific expression patterns and immune infiltration in the tumor microenvironment.

## Abstract

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.

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.

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.

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.

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.

## Linked entities

- **Genes:** FUOM (fucose mutarotase) [NCBI Gene 282969]
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, ASPM (assembly factor for spindle microtubules) [NCBI Gene 259266] {aka ASP, Calmbp1, MCPH5}, CYP1B1 (cytochrome P450 family 1 subfamily B member 1) [NCBI Gene 1545] {aka ASGD6, CP1B, CYPIB1, GLC3A, P4501B1}, ATP8B4 (ATPase phospholipid transporting 8B4 (putative)) [NCBI Gene 79895] {aka ATPIM}, PFKP (phosphofructokinase, platelet) [NCBI Gene 5214] {aka ATP-PFK, PFK-C, PFK-P, PFKF}, FANCD2 (FA complementation group D2) [NCBI Gene 2177] {aka FA-D2, FA4, FACD, FAD, FAD2, FANCD}, DCBLD2 (discoidin, CUB and LCCL domain containing 2) [NCBI Gene 131566] {aka CLCP1, ESDN}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CSTF2 (cleavage stimulation factor subunit 2) [NCBI Gene 1478] {aka CSTF64, CstF-64, XLID113}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCL28 (C-C motif chemokine ligand 28) [NCBI Gene 56477] {aka CCK1, MEC, SCYA28}, LAP (Laryngeal adductor paralysis) [NCBI Gene 7939], CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363] {aka CKb11, ELC, MIP-3b, MIP3B, SCYA19}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}, IL18R1 (interleukin 18 receptor 1) [NCBI Gene 8809] {aka CD218a, CDw218a, IL-18R, IL-18R-alpha, IL-18Ralpha, IL-1Rrp}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, FUOM (fucose mutarotase) [NCBI Gene 282969] {aka C10orf125, FUCU, FucM}, LEF1 (lymphoid enhancer binding factor 1) [NCBI Gene 51176] {aka ECTD1, ECTD17, LEF-1, TCF10, TCF1ALPHA, TCF7L3}, LAMTOR4 (late endosomal/lysosomal adaptor, MAPK and MTOR activator 4) [NCBI Gene 389541] {aka C7orf59}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, HCG22 (HLA complex group 22) [NCBI Gene 285834] {aka PBMUCL2}, PRKCQ (protein kinase C theta) [NCBI Gene 5588] {aka PRKCT, nPKC-theta}, MORN3 (MORN repeat containing 3) [NCBI Gene 283385], MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, CD70 (CD70 molecule) [NCBI Gene 970] {aka CD27-L, CD27L, CD27LG, LPFS3, TNFSF7, TNLG8A}, FGF19 (fibroblast growth factor 19) [NCBI Gene 9965]
- **Diseases:** HPV infection (MESH:D030361), endocervical adenocarcinoma (MESH:D000230), precancerous lesions (MESH:D011230), invasive cancer (MESH:D009362), infection (MESH:D007239), cancer (MESH:D009369), diabetes (MESH:D003920), tumorigenesis (MESH:D063646), Inflammatory (MESH:D007249), HMDD (MESH:D004194), chronic (MESH:D002908), cardiovascular disease (MESH:D002318), cervical squamous cell carcinoma (MESH:D002294), Cervical Cancer (MESH:D002583)
- **Chemicals:** paraformaldehyde (MESH:C003043), CO2 (MESH:D002245), DMEM (-), TRIzol (MESH:C411644), tryptophan (MESH:D014364), Formazan (MESH:D005562), crystal violet (MESH:D005840), streptomycin (MESH:D013307), DMSO (MESH:D004121), water (MESH:D014867), penicillin (MESH:D010406), Lipofectamine (MESH:C086724), MTT (MESH:C070243)
- **Species:** Human papillomavirus (species) [taxon 10566], Human papillomavirus 16 (serotype) [taxon 333760], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12357170/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12357170/full.md

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Source: https://tomesphere.com/paper/PMC12357170