WTAP mediates FOXP3 mRNA stability to promote SMARCE1 expression and augment glycolysis in colon adenocarcinoma

Tian, Xiaoxiao; Bai, Yanli; Liu, Xianmin; Zhu, Jihong; Zhang, Lamei; Wang, Jinliang

doi:10.1007/s00335-022-09962-z

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…Additionally, through RIP and MERIP experiments, we established a direct interaction between WTAP and ULK1, clarifying WTAP's role in modulating the m6A modification level of ULK1 mRNA. Prior studies have indicated that WTAP can regulate the mRNA stability of its target genes [37][38][39][40][41]. In line with these findings, our study also showed that WTAP affects the stability of ULK1 mRNA.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

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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“… 237 In Colon adenocarcinoma (COAD), WTAP stabilizes FOXP3 mRNA via YTHDF1, and FOXP3 bound to SMARCE1 promoter to exert transcriptional activation. 238 In CRC, WTAP modifies NT5DC3 to suppress the tumorigenesis under hyperglycemia via repressing Hexokinase domain component 1 (HKDC1). 239 Besides, writer KIAA1429 upregulates HK2 and GLUT1 level in methyltransferase activity-dependent manner, facilitating glycolytic process of CRC and GC, 240 , 241 and RBM15 catalyzes m6A modification to accelerate expression of HK2, glucose-6-phosphate isomerase (GPI) and phosphoglycerate kinase1 (PGK1) in OS, 242 while ZC3H13 significantly destabilizes PKM2 mRNA to weaken glycolytic reprogramming and enhance cisplatin sensitivity of HCC.…”

Section: Rna Modifications and Cellular Metabolismmentioning

confidence: 99%

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Liu,

Zheng,

et al. 2024

Sig Transduct Target Ther

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Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

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“…Zhang et al found that WTAP and YTHDF1 enhance the stability of FOXP3 mRNA in an m6A-dependent manner. High expression of FOXP3 can directly promote downstream glycolysis processes, and can also play a role in promoting glycolysis and proliferation of colon adenocarcinoma by increasing the expression of SMARCE1 [ 112 ].…”

Section: M6a Regulates Tumor Glycolysismentioning

confidence: 99%

m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism

Liu

Luo

et al. 2023

Mol Cancer

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Glycolytic reprogramming is one of the most important features of cancer and plays an integral role in the progression of cancer. In cancer cells, changes in glucose metabolism meet the needs of self-proliferation, angiogenesis and lymphangiogenesis, metastasis, and also affect the immune escape, prognosis evaluation and therapeutic effect of cancer. The n6-methyladenosine (m6A) modification of RNA is widespread in eukaryotic cells. Dynamic and reversible m6A modifications are widely involved in the regulation of cancer stem cell renewal and differentiation, tumor therapy resistance, tumor microenvironment, tumor immune escape, and tumor metabolism. Lately, more and more evidences show that m6A modification can affect the glycolysis process of tumors in a variety of ways to regulate the biological behavior of tumors. In this review, we discussed the role of glycolysis in tumor genesis and development, and elaborated in detail the profound impact of m6A modification on different tumor by regulating glycolysis. We believe that m6A modified glycolysis has great significance and potential for tumor treatment.

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WTAP mediates FOXP3 mRNA stability to promote SMARCE1 expression and augment glycolysis in colon adenocarcinoma

Cited by 7 publications

References 39 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

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism

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