The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m<sup>6</sup>A readers in cancer

Sun, Chen; Cao, Dengqing; Du, Bin; Chen, Cunwu; Liu, Dong

doi:10.7150/ijbs.70458

Cited by 42 publications

(26 citation statements)

References 197 publications

(225 reference statements)

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“…According to the literature, the IGF2BP protein family can bind m6A-modified mRNA and play an essential role in RNA stability [ 36 ]. Therefore, we used siRNA to knock down IGF2BP1/2/3 in the A2780 cell line and observed changes in SNAI1 mRNA expression.…”

Section: Resultsmentioning

confidence: 99%

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Sun¹,

Zhang²,

Bi³

et al. 2022

Cancers

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Fat mass and obesity-associated protein (FTO) regulates critical pathways in various diseases, including malignant tumours. However, the functional link between FTO and its target genes in epithelial ovarian cancer (EOC) development remains to be elucidated. In this study, the biological functions of FTO were verified in vitro and in vivo. The m6A modification and the binding sites of SNAI1 mRNA were confirmed by m6A RNA immunoprecipitation (MeRIP) and RIP experiments. The actinomycin D assay was used to test the stability of RNA. We found that FTO was downregulated with increased m6A levels in EOC. Reduced expression of FTO was associated with a higher FIGO stage in patients with EOC. Mechanistically, FTO decreased the m6A level and stability of SNAI1 mRNA, causing downregulation of SNAI1 and inhibiting epithelial–mesenchymal transition (EMT). Furthermore, FTO-mediated downregulation of SNAI1 expression depended on IGF2BP2, which acted as an m6A reader binding to the 3′ UTR region of SNAI1 mRNA to promote its stability. In conclusion, FTO inhibits SNAI1 expression to attenuate the growth and metastasis of EOC cells in an m6A-IGF2BP2-dependent manner. Our findings suggest that the FTO-IGF2BP2-SNAI1 axis is a potential therapeutic target in EOC.

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Section: Resultsmentioning

confidence: 99%

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Sun¹,

Zhang²,

Bi³

et al. 2022

Cancers

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“…Thus, IGF2BP1 is capable of promoting BC distant metastasis (Figure 7C). IGF2BP1 is regarded as a classic RNA-binding protein involved in the regulation of gene expression [51,52]. Recent evidence has confirmed that IGF2BP1 can function as an m6A reader to recognize m6A sites and enhance targeted mRNA stability [23].…”

Section: Discussionmentioning

confidence: 99%

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner

Shi¹,

Yin²,

Ye³

et al. 2023

Int. J. Biol. Sci.

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Metastasis leads to the vast majority of breast cancer mortality. Increasing evidence has shown that N6-methyladenosine (m6A) modification and its associated regulators play a pivotal role in breast cancer metastasis. Here, we showed that overexpression of the m6A reader IGF2BP1 was clinically correlated with metastasis in breast cancer patients. Moreover, IGF2BP1 promoted distant metastasis in vitro and in vivo. Mechanistically, we first identified USP10 as the IGF2BP1 deubiquitinase. USP10 can bind to, deubiquitinate, and stabilize IGF2BP1, resulting in its higher expression level in breast cancer. Furthermore, by MeRIP-seq and experimental verification, we found that IGF2BP1 directly recognized and bound to the m6A sites on CPT1A mRNA and enhanced its stability, which ultimately mediated IGF2BP1-induced breast cancer metastasis. In clinical samples, USP10 levels correlated with IGF2BP1 and CPT1A levels, and breast cancer patients with high levels of USP10, IGF2BP1, and CPT1A had the worst outcome. Therefore, these findings suggest that the USP10/IGF2BP1/CPT1A axis facilitates breast cancer metastasis, and this axis may be a promising prognostic biomarker and therapeutic target for breast cancer.

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“…IGF2BPs influence gene regulation and cancer biology by enhancing the stability and storage of their target mRNAs. IGF2BP1 is a conserved oncogenic driver with significantly upregulated expression in various types of cancer ( 129 , 130 ).…”

Section: M6a and Ecmentioning

confidence: 99%

RNA m6A methylation regulators in endometrial cancer (Review)

Shen

Guo

et al. 2022

Int J Oncol

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As one of the three major malignant tumor types of the female reproductive system, endometrial cancer (EC) is the most prevalent gynecologic cancer in developed countries. In recent years, the incidence of EC has increased worldwide, threatening the health and well-being of women. Recent research has indicated that the expression of multiple N6-methyladenosine (m6A) regulators is up-or downregulated in EC and that abnormalities in m6A methylation and the expression of associated regulators are critical to the pathogenesis and progression of EC. m6A is the most abundant internal modification of mRNA. Several studies have demonstrated a close association between the development and progression of malignant tumors and the epigenetic phenomenon of m6A methylation. In the present study, the current status of research on m6A methylation in EC was reviewed. The mechanisms of methyltransferase, demethylase and m6A binding protein in regulating the development and progression of EC by modifying mRNA were introduced. The related research results will provide novel methods and approaches for the prevention and treatment of EC.

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Cited by 42 publications

References 197 publications

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner

RNA m6A methylation regulators in endometrial cancer (Review)

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

Cited by 42 publications

References 197 publications

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner

RNA m6A methylation regulators in endometrial cancer (Review)

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer