IGF2BPs as novel m6A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Duan, Meiqi; Liu, Haiyang; Yang, Zhi; Zhang, Fusheng; Wang, Guang; Wang, Yutian; Zhao, Shan; Jiang, Xiaofeng

doi:10.1016/j.gendis.2023.06.017

Cited by 18 publications

(3 citation statements)

References 298 publications

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“…m6A modification typically necessitates recognition by specific readers to manifest its effects. Previous research has identified IGF2BPs as readers that regulate mRNA stability [31,[42][43][44]. In our study, we employed siRNAs to knock down the expression of IGF2BP1/2/3 and observed a significant decrease in ULK1 expression following the knockdown of IGF2BP3.…”

Section: Discussionmentioning

confidence: 79%

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Wang,

Zheng,

Wang

et al. 2024

Cell Death Dis

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There is a pressing need for innovative therapeutic strategies for patients with epithelial ovarian cancer (EOC). Previous studies have shown that UNC-51-like kinase 1 (ULK1), a serine/threonine kinase, is crucial in regulating cellular autophagy and mitophagy across various tumor types. However, the clinical implications, biological functions, and potential mechanisms of ULK1 in EOC remain poorly understood. This study demonstrates that ULK1 expression is upregulated in EOC tissue samples and EOC cell lines, with increased ULK1 expression correlating with poor prognosis. Functionally, overexpressed ULK1 enhances the proliferation and migration abilities of EOC cells both in vitro and in vivo. Mechanistically, ULK1 was identified as an m6A target of WTAP. WTAP-mediated m6A modification of ULK1 enhanced its mRNA stability in an IGF2BP3-dependent manner, leading to elevated ULK1 expression and enhanced mitophagy in EOC. In summary, our research reveals that the WTAP/IGF2BP3-ULK1 axis significantly influences protective mitophagy in EOC, contributing to its progression. Therefore, the regulatory mechanisms and biological function of ULK1 identify it as a potential molecular target for therapeutic intervention in EOC.

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Section: Discussionmentioning

confidence: 79%

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Wang,

Zheng,

Wang

et al. 2024

Cell Death Dis

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“…The equilibrium of oxygen content in extracellular fluid is crucial for cell survival and normal metabolism ( Tao et al, 2021 ). Under severe hypoxic stress, cells precisely regulate the expression of certain coding genes or non-coding RNA through oxygen receptors and signal transduction, thereby participating in a variety of physiological and pathological processes ( Duan et al, 2024 ). The hypoxia-inducible factors are members of the basic helix-loop-helix Per-Arnt-Sim transcription factor superfamily.…”

Section: Biological Characteristics and Functions Of Hif-1αmentioning

confidence: 99%

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

Zhou,

Lan,

Liu

et al. 2024

Front. Pharmacol.

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Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

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“…IGF2BP1 binds to target mRNAs to regulate their stability, translation and/or localization (43,44). More recently, the family of IGF2BPs was shown to recognize RNAs in a N6methyladenosine (m 6 A)-dependent manner and is considered as m 6 A readers (44,45). IGF2BP1 is viewed as a promising target in cancer therapy since many of its targets are involved in cancer growth and development.…”

Section: Introductionmentioning

confidence: 99%

APE1 associates with 60S ribosomes and tRNAs and regulates the expression of IGF2BP1

Li,

Tafech,

Lee

2023

Preprint

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Apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional protein known for its DNA repair function and redox regulation, is often found overexpressed in cancers. APE1 can be found in the nucleus, cytoplasm and secreted extracellularly. APE1 subcellular distribution in the cytoplasm is frequently reported in various types of cancer but the biological significance remains unknown. In this study, APE1 in the cytoplasm of HepG2 cells was investigated using various techniques including microscopy, differential centrifugation, sucrose gradient fractionation and CL-IP. APE1 was found to associate with 60S ribosomes and tRNAs under native conditions, suggesting it may have a specific function in the translational machinery. Knockdown of APE1 in HepG2 cells led to increased protein expression of IGF2BP1 as well as enhanced HepG2 cell migration, suggesting that APE1 can act as a tumor suppressor in this cell line model of hepatocellular carcinoma. When APE1 was depleted, the translation of a reporter construct containing the 3’UTR of IGF2BP1 was enhanced. This study provides evidence in support of the role of cytoplasmic APE1 in the control of IGF2BP1 protein translation and sheds light on the potential novel function of cytoplasmic APE1.

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IGF2BPs as novel m6A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Cited by 18 publications

References 298 publications

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

APE1 associates with 60S ribosomes and tRNAs and regulates the expression of IGF2BP1

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