<scp>YTHDF3</scp> mediates <scp>HNF1α</scp> regulation of cervical cancer radio‐resistance by promoting <scp>RAD51D</scp> translation in an <scp>m6A</scp>‐dependent manner

Du, Hui; Zou, Naiyi; Zuo, Hongling; Zhang, Xueyuan; Zhu, Shuchai

doi:10.1111/febs.16681

Cited by 19 publications

(16 citation statements)

References 50 publications

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“…This regulatory mechanism involving YTHDF3-mediated HR pathway-based DNA damage repair contributes to the modulation of radiation resistance in cervical cancer ( Figure 2B ). The blockage of this pathway may offer therapeutic benefits for enhancing radiation tolerance by specifically targeting cervical cancer ( 18 ).…”

Section: Dna Damage Repairmentioning

confidence: 99%

The research progress on radiation resistance of cervical cancer

Liang,

Sheng,

et al. 2024

Front. Oncol.

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Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as the fourth most common cancer worldwide, thus posing a significant threat to the lives and health of women. Advanced and early-stage cervical carcinoma patients with high-risk factors require adjuvant treatment following surgery, with radiotherapy being the primary approach. However, the tolerance of cervical cancer to radiotherapy has become a major obstacle in its treatment. Recent studies have demonstrated that radiation resistance in cervical cancer is closely associated with DNA damage repair pathways, the tumor microenvironment, tumor stem cells, hypoxia, cell cycle arrest, and epigenetic mechanisms, among other factors. The development of tumor radiation resistance involves complex interactions between multiple genes, pathways, and mechanisms, wherein each factor interacts through one or more signaling pathways. This paper provides an overview of research progress on an understanding of the mechanism underlying radiation resistance in cervical cancer.

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Section: Dna Damage Repairmentioning

confidence: 99%

The research progress on radiation resistance of cervical cancer

Liang,

Sheng,

et al. 2024

Front. Oncol.

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“…According to reports, YTHDF3 plays a pivotal role as a key component of m 6 a methylation in various tumor types [32][33][34][35] . Previous studies have also emphasized the involvement of YTHDF3 in brain metastasis of breast cancer cells 15 , as well as its signi cant role in the progression and metastasis of triple-negative breast cancer through the YTHDF3-ZEB1 axis 34 .…”

Section: Discussionmentioning

confidence: 99%

YTHDF3 modulates the progression of breast cancer cells by regulating FGF2 through m6A methylation

Gong,

Zhang,

Sun

et al. 2023

Preprint

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Background Breast cancer (BC) is a prevailing malignancy among women, and its inconspicuous development contributes significantly to mortality. The RNA N6-methyladenosine (m6A) modification represents an emerging mechanism for gene expression regulation, with the active involvement of the YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) in tumor progression across multiple cancer types. Nonetheless, its precise function in breast cancer necessitates further investigation. Methods The expression of YTHDF3 in both cell lines and patient tissues was examined using Western blotting, reverse transcription quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) techniques. Bioinformatics analysis of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome RNA sequencing (RNA-seq) data was employed to screen for the target genes of YTHDF3. The main focus of this study was to investigate the in vitro biological functions of YTHDF3. The specific binding of YTHDF3 to its target genes and its correlation with m6A methylation were studied through RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation experiments. The protein regulatory mechanisms of downstream genes of YTHDF3 were assessed using protein stability analysis. Furthermore, the biological functions of YTHDF3 and its target genes in breast cancer cells were validated through CRISPR-Cas9 technology and rescue experiments. Results By constructing a risk model using the TCGA database, YTHDF3 was identified as a high-risk factor among m6A methylation factors. Subsequent investigations revealed its elevated expression in various subtypes of breast cancer, accompanied by poor prognosis. MeRIP-seq analysis further revealed fibroblast growth factor 2 (FGF2) as a downstream gene of YTHDF3. Knockdown of YTHDF3 in breast cancer cells led to significant inhibition of cell self-renewal, migration, and invasion abilities in vitro. Mechanistically, YTHDF3 specifically recognized the methylated transcript of FGF2 within its coding sequence (CDS) region, leading to the inhibition of FGF2 protein degradation. Moreover, depletion of FGF2 markedly suppressed the biological functions of breast cancer cells, while reducing FGF2 expression in YTHDF3-overexpressing breast cancer cell lines substantially alleviated the malignant progression. Conclusions In summary, our study elucidates the role of YTHDF3 as an oncogene in maintaining FGF2 expression in BC cells through an m6A-dependent mechanism. Additionally, we provide a potential biomarker panel for prognostic prediction in BC.

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“…Mechanistically, YTHDF3 promotes RAD51D translation and YTHDC2 activates the IGF1R/ATK/S6 signalling axis, both in an m6A-dependent manner. 134,135 The IGF2BPs also mediate chemoresistance. Overexpression of IGF2BP1 mediates doxorubicin resistance via stabilising the mRNA of oestrogen-related receptor alpha (ERRα) and ABCB1.…”

Section: Players In Chemoresistancementioning

confidence: 99%

“…Apart from chemoresistance, YTHDF3 and YTHDC2 correlate with radiotherapy resistance in cervical cancer and nasopharyngeal carcinoma. Mechanistically, YTHDF3 promotes RAD51D translation and YTHDC2 activates the IGF1R/ATK/S6 signalling axis, both in an m6A‐dependent manner 134,135 …”

Section: M6a Regulators Are Key Players In Chemoresistancementioning

confidence: 99%

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Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Guan,

Wong

2024

Cancer Medicine

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The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising RNA methylation have been identified. Notably, these m6A regulators often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, the complex roles of these regulators in human cancer pathology remain enigmatic, with conflicting outcomes reported in different studies.In recent years, a multitude of inhibitors and activators targeting m6A regulators have been reported. Several of these compounds have demonstrated promising efficacy in both in vitro and in vivo cancer models. These findings collectively underscore the dynamic landscape of m6A regulation in cancer biology, revealing its potential as a therapeutic target and prognostic indicator.

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YTHDF3 mediates HNF1α regulation of cervical cancer radio‐resistance by promoting RAD51D translation in an m6A‐dependent manner

Cited by 19 publications

References 50 publications

The research progress on radiation resistance of cervical cancer

The research progress on radiation resistance of cervical cancer

YTHDF3 modulates the progression of breast cancer cells by regulating FGF2 through m6A methylation

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

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