Inhibition of the m6A Reader IGF2BP2 Impairs Cell Cycle Progression and Glycolysis in Ovarian Cancer

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and plays a crucial role in regulating mRNA stability, translation, and degradation. Dysregulation of m6A regulators has been increasingly implicated in cancer, yet their cell type–specific roles and therapeutic value in ovarian cancer remain clearly unexplored. We conducted an integrative analysis of single-cell and bulk RNA sequencing datasets from ovarian tumors and matched non-malignant tissues to identify m6A regulators associated with tumor progression. Functional experiments, including gene knockdown, flow cytometry, metabolic assays, and RIP-seq analysis, were performed to evaluate the role of candidate regulators. A small-molecule inhibitor of IGF2BP2 (CWI1-2) was also used to assess therapeutic potential in ovarian cancer cell lines. IGF2BP2 was identified as the most significantly upregulated m6A reader in malignant epithelial cells and was associated with poor patient prognosis. Knockdown of IGF2BP2 impaired cell proliferation, induced cell cycle arrest and apoptosis, and suppressed glycolytic activity. RIP-seq data revealed that IGF2BP2 directly binds transcripts of key oncogenes including CDK4, BCL2L2, and SLC2A1, thereby stabilizing their expression. Pharmacological inhibition of IGF2BP2 recapitulated the effects of genetic silencing, confirming its essential role in sustaining oncogenic programs in ovarian cancer cells. Our findings establish IGF2BP2 as a critical m6A reader that post-transcriptionally regulates gene networks driving proliferation, survival, and metabolic reprogramming in ovarian cancer. Targeting IGF2BP2 may represent a promising therapeutic strategy for m6A-based precision oncology in ovarian cancer.

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Journal
Molecular Biology
Published
2026-01-20
DOI
https://doi.org/10.1134/s0026893325700694
Primary Topic
RNA modifications and cancer
Type
article
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0.00
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article

Inhibition of the m6A Reader IGF2BP2 Impairs Cell Cycle Progression and Glycolysis in Ovarian Cancer

Kaiyuan Ji, Zhiqiang Qin, Jie Hao, J. Liang et al.
Molecular Biology
RNA modifications and cancer
article

Inhibition of the m6A Reader IGF2BP2 Impairs Cell Cycle Progression and Glycolysis in Ovarian Cancer

Kaiyuan Ji, Zhiqiang Qin, Jie Hao, J. Liang, G. Zhu, J. Wang, X. Yang, J. Zhou
article en

Abstract

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and plays a crucial role in regulating mRNA stability, translation, and degradation. Dysregulation of m6A regulators has been increasingly implicated in cancer, yet their cell type–specific roles and therapeutic value in ovarian cancer remain clearly unexplored. We conducted an integrative analysis of single-cell and bulk RNA sequencing datasets from ovarian tumors and matched non-malignant tissues to identify m6A regulators associated with tumor progression. Functional experiments, including gene knockdown, flow cytometry, metabolic assays, and RIP-seq analysis, were performed to evaluate the role of candidate regulators. A small-molecule inhibitor of IGF2BP2 (CWI1-2) was also used to assess therapeutic potential in ovarian cancer cell lines. IGF2BP2 was identified as the most significantly upregulated m6A reader in malignant epithelial cells and was associated with poor patient prognosis. Knockdown of IGF2BP2 impaired cell proliferation, induced cell cycle arrest and apoptosis, and suppressed glycolytic activity. RIP-seq data revealed that IGF2BP2 directly binds transcripts of key oncogenes including CDK4, BCL2L2, and SLC2A1, thereby stabilizing their expression. Pharmacological inhibition of IGF2BP2 recapitulated the effects of genetic silencing, confirming its essential role in sustaining oncogenic programs in ovarian cancer cells. Our findings establish IGF2BP2 as a critical m6A reader that post-transcriptionally regulates gene networks driving proliferation, survival, and metabolic reprogramming in ovarian cancer. Targeting IGF2BP2 may represent a promising therapeutic strategy for m6A-based precision oncology in ovarian cancer.

Molecular Biology
Guangzhou Women and Children Medical Center (CN), Guangxi University of Chinese Medicine (CN), Guangzhou Medical University Cancer Hospital (CN), Guangzhou Medical University (CN)
Good health and well-being
Openalex Percentile: Top 84%
RNA modifications and cancer
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