# Differentially Expressed Genes Associated with the Development of Cervical Cancer

**Authors:** Diego Armando Alvarado-Camacho, Ricardo Castillo-Velázquez, Angelica Judith Granados-López, Hiram Hernández-López, Yamilé López-Hernández, Rosalinda Gutiérrez-Hernández, José Antonio Varela-Silva, Claudia Araceli Reyes-Estrada, Cesar Rogelio Solorio-Alvarado, Sergio Hugo Sánchez-Rodríguez, David Alejandro García-López, Jesús Adrián López

PMC · DOI: 10.3390/ijms27010258 · International Journal of Molecular Sciences · 2025-12-26

## TL;DR

This study identifies genes linked to cervical cancer development, which could help in diagnosis and treatment.

## Contribution

The paper identifies novel differentially expressed genes and miRNA associations in cervical cancer.

## Key findings

- Several genes were found to be significantly upregulated or downregulated in cervical cancer.
- Key transcription factors and hub proteins were identified as potential biomarkers.
- Multiple miRNAs were found to potentially regulate hub proteins associated with cervical cancer.

## Abstract

Cervical cancer remains a significant cause of cancer-related mortality among women, particularly in low- and middle-income countries. High-throughput technologies, such as microarrays, have facilitated the comprehensive analysis of gene expression profiles in cervical cancer, enabling the identification of key differentially expressed genes (DEGs) involved in its pathogenesis. The publicly available microarray datasets, including GSE39001, GSE9750, GSE7803, GSE6791, GSE63514, and GSE52903 in combination with bioinformatics database predictions, were used to identify differential expression genes, potential biomarkers, and therapeutic targets for cervical cancer; additionally, we undertook bioinformatic analysis to determine gene ontology and possible miRNA targets related to our DEGs. Our analysis revealed several DEGs significantly associated with cervical cancer progression, such as cell death, regulation of DNA replication, protein binding processes, and transcription factors. The most relevant transcription factors (TFs) identified were SP1, ELF3, E2F1, TP53, RELA, HDAC, and FOXM1. Importantly, the DEGs with more important changes were 11 coding genes that were upregulated (KIF4A, MCM5, RFC4, PLOD2, MMP12, PRC1, TOP2A, MCM2, RAD51AP1, KIF20A, AIM2) and 14 that were downregulated (CXCL14, KRT1, KRT13, MAL, SPINK5, EMP1, CRISP3, ALOX12, CRNN, SPRR3, PPP1R3C, IVL, CFD, CRCT1), which were associated with cervical cancer. Interestingly, hub proteins KIF4A, NUSAP1, BUB1B, CEP55, DLGAP5, NCAPG, CDK1, MELK, KIF11, and KIF20A were found to be potentially regulated by several miRNAs, including miR-107, miR-124-3p, miR-147a, miR-16-5p, miR-34a-5p, miR-34c-5p, miR-126-3p, miR-10b-5p, miR-23b-3p, miR-200b-3p, miR-138-5p, miR-203a-3p, miR-214-3p, and let-7b-5p. The relationship between these genes highlights their potential as candidate biomarkers for further research in treatment, diagnosis, and prognosis.

## Linked entities

- **Genes:** KIF4A (kinesin family member 4A) [NCBI Gene 24137], MCM5 (minichromosome maintenance complex component 5) [NCBI Gene 4174], RFC4 (replication factor C subunit 4) [NCBI Gene 5984], PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) [NCBI Gene 5352], MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321], PRC1 (protein regulator of cytokinesis 1) [NCBI Gene 9055], TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153], MCM2 (minichromosome maintenance complex component 2) [NCBI Gene 4171], RAD51AP1 (RAD51 associated protein 1) [NCBI Gene 10635], KIF20A (kinesin family member 20A) [NCBI Gene 10112], AIM2 (absent in melanoma 2) [NCBI Gene 9447], CXCL14 (C-X-C motif chemokine ligand 14) [NCBI Gene 9547], KRT1 (keratin 1) [NCBI Gene 3848], KRT13 (keratin 13) [NCBI Gene 3860], MAL (mal, T cell differentiation protein (MAL blood group)) [NCBI Gene 4118], SPINK5 (serine peptidase inhibitor Kazal type 5) [NCBI Gene 11005], EMP1 (epithelial membrane protein 1) [NCBI Gene 2012], CRISP3 (cysteine rich secretory protein 3) [NCBI Gene 10321], ALOX12 (arachidonate 12-lipoxygenase, 12S type) [NCBI Gene 239], CRNN (cornulin) [NCBI Gene 49860], SPRR3 (small proline rich protein 3) [NCBI Gene 6707], PPP1R3C (protein phosphatase 1 regulatory subunit 3C) [NCBI Gene 5507], IVL (involucrin) [NCBI Gene 3713], CFD (complement factor D) [NCBI Gene 1675], CRCT1 (cysteine rich C-terminal 1) [NCBI Gene 54544]
- **Proteins:** SP1 (Sp1 transcription factor), ELF3 (E74 like ETS transcription factor 3), E2F1 (E2F transcription factor 1), TP53 (tumor protein p53), RELA (RELA proto-oncogene, NF-kB subunit), HDAC9 (histone deacetylase 9), FOXM1 (forkhead box M1), KIF4A (kinesin family member 4A), NUSAP1 (nucleolar and spindle associated protein 1), BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B), CEP55 (centrosomal protein 55), DLGAP5 (DLG associated protein 5), NCAPG (non-SMC condensin I complex subunit G), CDK1 (cyclin dependent kinase 1), MELK (maternal embryonic leucine zipper kinase), KIF11 (kinesin family member 11), KIF20A (kinesin family member 20A)
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** PPP1R3C (protein phosphatase 1 regulatory subunit 3C) [NCBI Gene 5507] {aka PPP1R5, PTG}, SPRR3 (small proline rich protein 3) [NCBI Gene 6707], NUSAP1 (nucleolar and spindle associated protein 1) [NCBI Gene 51203] {aka ANKT, BM037, LNP, NUSAP, PRO0310p1, Q0310}, SPINK5 (serine peptidase inhibitor Kazal type 5) [NCBI Gene 11005] {aka LEKTI, LETKI, NETS, NS, VAKTI}, KIF11 (kinesin family member 11) [NCBI Gene 3832] {aka EG5, HKSP, KNSL1, MCLMR, TRIP5}, CRNN (cornulin) [NCBI Gene 49860] {aka C1orf10, PDRC1, SEP53}, MAL (mal, T cell differentiation protein (MAL blood group)) [NCBI Gene 4118] {aka HLD28, MVP17, VIP17}, FOXM1 (forkhead box M1) [NCBI Gene 2305] {aka FKHL16, FOXM1A, FOXM1B, FOXM1C, HFH-11, HFH11}, KRT1 (keratin 1) [NCBI Gene 3848] {aka AEI2, CK1, EHK, EHK1, EPPK, K1}, BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) [NCBI Gene 701] {aka BUB1beta, BUBR1, Bub1A, MAD3L, MVA1, SSK1}, DLGAP5 (DLG associated protein 5) [NCBI Gene 9787] {aka DLG7, HURP}, MELK (maternal embryonic leucine zipper kinase) [NCBI Gene 9833] {aka HPK38}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321] {aka HME, ME, MME, MMP-12}, CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, CFD (complement factor D) [NCBI Gene 1675] {aka ADIPSIN, ADN, DF, PFD}, MIR10B (microRNA 10b) [NCBI Gene 406903] {aka MIRN10B, hsa-mir-10b, miRNA10B, mir-10b}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, AIM2 (absent in melanoma 2) [NCBI Gene 9447] {aka PYHIN4}, MIR34C (microRNA 34c) [NCBI Gene 407042] {aka MIRN34C, miRNA34C, mir-34c}, TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153] {aka TOP2, TOP2alpha, TOPIIA, TP2A}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, CEP55 (centrosomal protein 55) [NCBI Gene 55165] {aka C10orf3, CT111, MARCH, URCC6}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, GDE1 (glycerophosphodiester phosphodiesterase 1) [NCBI Gene 51573] {aka 363E6.2, MIR16}, MIR23B (microRNA 23b) [NCBI Gene 407011] {aka MIRN23B, hsa-mir-23b, miRNA23B, mir-23b}, ALOX12 (arachidonate 12-lipoxygenase, 12S type) [NCBI Gene 239] {aka 12-LOX, 12S-LOX, LOG12}, MIR107 (microRNA 107) [NCBI Gene 406901] {aka MIRN107, miR-107}, PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) [NCBI Gene 5352] {aka BRKS2, LH2, TLH}, ELF3 (E74 like ETS transcription factor 3) [NCBI Gene 1999] {aka EPR-1, ERT, ESE-1, ESX}, MCM5 (minichromosome maintenance complex component 5) [NCBI Gene 4174] {aka CDC46, MGORS8, P1-CDC46}, CRISP3 (cysteine rich secretory protein 3) [NCBI Gene 10321] {aka Aeg2, CRISP-3, CRS3, SGP28, dJ442L6.3}, RAD51AP1 (RAD51 associated protein 1) [NCBI Gene 10635] {aka PIR51}, RFC4 (replication factor C subunit 4) [NCBI Gene 5984] {aka A1, MRMNS, RFC37}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], MIR203A (microRNA 203a) [NCBI Gene 406986] {aka MIR203, MIRN203, hsa-mir-203a, miR-203, miRNA203, mir-203a}, CRCT1 (cysteine rich C-terminal 1) [NCBI Gene 54544] {aka C1orf42, NICE-1, NICE1}, CXCL14 (C-X-C motif chemokine ligand 14) [NCBI Gene 9547] {aka BMAC, BRAK, KEC, KS1, MIP-2g, MIP2G}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, PRC1 (protein regulator of cytokinesis 1) [NCBI Gene 9055] {aka ASE1, MAP65}, MIR200B (microRNA 200b) [NCBI Gene 406984] {aka MIRN200B, mir-200b}, MCM2 (minichromosome maintenance complex component 2) [NCBI Gene 4171] {aka BM28, CCNL1, CDCL1, D3S3194, DFNA70, MITOTIN}, KRT13 (keratin 13) [NCBI Gene 3860] {aka CK13, K13, WSN2}, KIF4A (kinesin family member 4A) [NCBI Gene 24137] {aka KIF4, KIF4G1, MRX100, TMDI, XLID100}, EMP1 (epithelial membrane protein 1) [NCBI Gene 2012] {aka CL-20, EMP-1, TMP}, NCAPG (non-SMC condensin I complex subunit G) [NCBI Gene 64151] {aka CAPG, CHCG, NY-MEL-3, YCG1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, KIF20A (kinesin family member 20A) [NCBI Gene 10112] {aka MKLP2, RAB6KIFL, RCM6}, IVL (involucrin) [NCBI Gene 3713], MIR147A (microRNA 147a) [NCBI Gene 406939] {aka MIR147, MIRN147, hsa-mir-147a}
- **Diseases:** cancer (MESH:D009369), Cervical Cancer (MESH:D002583)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12786327/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12786327/full.md

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Source: https://tomesphere.com/paper/PMC12786327