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N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review)

  • Authors:
    • Man Xu
    • Fanglei Yang
    • Huan Chen
    • Feiyun Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, The Second People's Hospital of Wuhu City, Wuhu, Anhui 241000, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 442
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    Published online on: July 14, 2025
       https://doi.org/10.3892/ol.2025.15188
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Abstract

Cervical cancer is one of the most common malignant tumors among women worldwide. Its primary etiology is closely associated with human papillomavirus infection, which poses a serious threat to the health of women. N6‑methyladenosine (m6A) modifications notably affect the biological characteristics of tumor cells, such as their proliferation, metastasis and chemoresistance, by regulating the stability, translation and degradation of RNA. It also serves an important regulatory role in the pathogenesis of cervical cancer. The present review details the mechanisms underlying m6A modification in cervical cancer and analyzes its impact on tumor progression. Moreover, it explores the potential clinical applications of m6A modification as a biomarker and therapeutic target to provide new insights and evidence regarding the early diagnosis and individualized treatment of patients with cervical cancer.
View Figures

Figure 1

Dynamic regulatory mechanism of m6A
modification. Writers are responsible for adding m6A modifications
to mRNA, erasers for removing these modifications, and readers for
recognizing and responding to m6A modifications. These collectively
regulate gene expression and cellular functions. m6A,
N6-methyladenosine. WTAP, Wilms tumor 1-associated protein;
KIAA1429/VIRMA, Vir-like m6A methyltransferase associated;
RBM15/RBM15B, RNA binding motif protein 15/15B; METTL14,
methyltransferase like 14; ZC3H13, zinc finger CCCH-type containing
13; FTO, fat mass and obesity-associated protein; ALKBH5, AlkB
homolog 5; YTHDF1, YTH N6-methyladenosine RNA binding protein 1;
YTHDC1, YTH domain containing 1; HNRNPC, heterogeneous nuclear
ribonucleoprotein C; IGF2BP1, insulin-like growth factor 2
mRNA-binding protein 1.

Figure 2

In cervical cancer, writers and their
interacting readers jointly regulate target mRNA to promote or
inhibit the progression of cervical cancer. The readers include (A)
METTL3, (B) METTL14, (C) RBM15, (D) WTAP, KIAA1429 and ZC3H13.
METTL, methyltransferase; RBM15, RNA binding motif protein 15;
WTAP, WT1-associated protein; KIAA1429, Vir-like m6A
methyltransferase associated; ZC3H13, zinc finger CCCH-type
containing 13; TXNDC5, thioredoxin domain containing 5; PDE3A,
phosphodiesterase 3A; CTSL, cathepsin L; DDX6, DEAD-box helicase 6;
TAPBP, TAP binding protein; FTH1, ferritin heavy chain 1; EZH2,
enhancer of zeste 2 polycomb repressive complex 2 subunit; CENPK,
centromere protein K; CKAP2, cytoskeleton associated protein 2;
LARP1, La ribonucleoprotein 1.

Figure 3

Targets and signaling pathways of m6A
erasers in CC. The m6A erasers FTO and ALKBH5 dynamically regulate
CC progression by modulating distinct molecular targets and
signaling networks. m6A, N6-methyladenosine; FTO, fat mass and
obesity-associated protein; ALKBH5, AlkB homolog 5, RNA
demethylase; CC, cervical cancer. HIF1A, hypoxia-inducible factor 1
subunit alpha; CCDC134, Coiled-coil domain containing 134; GSK3β,
Glycogen synthase kinase 3β; E2F1, E2F transcription factor 1;
PAK5, P21 (RAC1) activated kinase 5.

Figure 4

m6A readers and related signaling
pathways in the development, metastasis and radioresistance of CC.
m6A readers affect tumor development, metastasis and
radioresistance via regulating downstream signaling pathways. The
Hippo/YAP, Wnt/β-catenin and PI3K/MAPK signaling pathways are all
highly activated and serve a role in the tumor cell proliferation,
differentiation and metastasis of CC cells. m6A,
N6-methyladenosine; CC, cervical cancer; NR4A1, nuclear receptor
subfamily 4 group A member 1; AKT1, AKT serine/threonine kinase 1;
SYVN, synoviolin; NLRP3, NLR family pyrin domain containing 3;
FOXM1, forkhead box M1; MAPK, mitogen-activated protein kinase;
FASN, fatty acid synthase.

Figure 5

Lollipop plot of the immune
infiltration profiles of the m6A regulators. A correlation analysis
was performed using the ggplot2 package between several m6A
regulators in the data and the immune infiltration matrix. m6A,
N6-methyladenosine. The immune cell types included T helper cells,
Th2 cells, Tcm, NK cells, Tem, eosinophils, mast cells, NK CD56
bright cells, CD8 T cells, Tgd, Tfh, macrophages, Th17 cells,
neutrophils, iDC, pDC, T cells, DC, aDC, NK CD56dim cells, B cells,
Treg, Th1 cells and cytotoxic cells. Treg, T-regulatory cells; Th2,
type 2 T-helper; NK, natural killer; DC, dendritic cells; aDC,
activated DC; iDC, interdigitating DC; pDC, plasmacytoid DC; Tcm,
central memory T-cells; Tem, effector memory T-cells; Tgd, gamma
delta T cells; Tfh, T follicular helper cells. *P<0.05,
**P<0.01 and ***P<0.001.
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Copy and paste a formatted citation
Spandidos Publications style
Xu M, Yang F, Chen H and Jiang F: N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review). Oncol Lett 30: 442, 2025.
APA
Xu, M., Yang, F., Chen, H., & Jiang, F. (2025). N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review). Oncology Letters, 30, 442. https://doi.org/10.3892/ol.2025.15188
MLA
Xu, M., Yang, F., Chen, H., Jiang, F."N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review)". Oncology Letters 30.3 (2025): 442.
Chicago
Xu, M., Yang, F., Chen, H., Jiang, F."N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review)". Oncology Letters 30, no. 3 (2025): 442. https://doi.org/10.3892/ol.2025.15188
Copy and paste a formatted citation
x
Spandidos Publications style
Xu M, Yang F, Chen H and Jiang F: N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review). Oncol Lett 30: 442, 2025.
APA
Xu, M., Yang, F., Chen, H., & Jiang, F. (2025). N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review). Oncology Letters, 30, 442. https://doi.org/10.3892/ol.2025.15188
MLA
Xu, M., Yang, F., Chen, H., Jiang, F."N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review)". Oncology Letters 30.3 (2025): 442.
Chicago
Xu, M., Yang, F., Chen, H., Jiang, F."N6‑methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review)". Oncology Letters 30, no. 3 (2025): 442. https://doi.org/10.3892/ol.2025.15188
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