METTL3 induces PLX4032 resistance in melanoma by promoting m6A-dependent EGFR translation

Bhattarai, Poshan Yugal; Kım, Garam; Poudel, Muna; Lim, Sung Chul; Choi, Hong Seok

doi:10.1016/j.canlet.2021.09.015

Cited by 35 publications

(23 citation statements)

References 39 publications

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“…Among the different RNA modifications, m6A remains the best characterized at the functional level and the most abundant modifications in mRNA ( Zaccara et al, 2019 ). METTL3, the first identified gene in m6A modification, can interact with Per2 and Arntl to directly mediate the export of mRNA ( Bhattarai et al, 2021 ). METTL14, METTL16, WTAP, VIRMA, ZC3H13, CBLL1, RBM15, and RBM15B are also included in the complex of m6A “writers” ( Meyer and Jaffrey, 2017 ; Wen et al, 2018 ; Gu et al, 2022 ; Shen et al, 2022 ; Su et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

et al. 2022

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N6-methyladenosine (m6A) modification plays a pivotal role in post-transcriptionally regulating gene expression and biological functions. Nonetheless, the roles of m6A modification in the regulation of chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remain unclear. Twenty-two significant m6A regulators were selected from differential gene analysis between the control and treatment groups from the GSE150910 dataset. Five candidate m6A regulators (insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, YTH domain-containing protein 1, zinc finger CCCH domain-containing protein 13, and methyltransferase-like 3) were screened by the application of a random forest model and nomogram model to predict risks of pulmonary fibrosis. The consensus clustering method was applied to divide the treatment samples into two groups with different m6A patterns (clusters A and B) based on the 22 m6A regulators. Our study performed principal component analysis to obtain the m6A-related score of the 288 samples to quantify the two m6A patterns. The study reveals that cluster A was linked to T helper cell (Th) 2-type cytokines, while the immune infiltration of Th1 cytokines was higher in cluster B. Our results suggest that m6A cluster A is likely related to pulmonary fibrosis, indicating m6A regulators play notable roles in the occurrence of pulmonary fibrosis. The m6A patterns could be considered as biomarkers to identify CHP and IPF, which will be helpful to develop immunotherapy strategies for pulmonary fibrosis in the future.

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Section: Introductionmentioning

confidence: 99%

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

et al. 2022

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“…BMPs have been defined as potentially significant in tumor etiology. BMP1 was involved in the excitation of the TGFβ and BMP signaling pathways [23,40]. Furthermore, overexpression of BMP1 was investigated in multifarious carcinomas, such as lung cancer, gastric cancer, and osteosarcoma [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, m6A is not only the most abundantly modified mRNA but also the best characterized at the functional level [22]. Since the discovery of the first gene in m6A modification, METTL3, other genes have been reported one after another, including m6A "writers" (METTL14, METTL16, WTAP, VIRMA, ZC3H13, CBLL1, RBM15, and RBM15B), m6A "readers" (YTHDC1-2, YTHDF1-3, HNRNPC, FMR1, LRPPRC, HNRNPA2B1, IGFBP1-3, RBMX, ELAVL1, and IGF2BP1), and m6A "erasers" (FTO and ALKBH5) [23][24][25][26][27][28]. Nevertheless, the relationship between m6A regulators and BMP1 expression in pancancer is unclear.…”

Section: Introductionmentioning

confidence: 99%

An Analysis of BMP1 Associated with m6A Modification and Immune Infiltration in Pancancer

Zhou

Sun

et al. 2022

Disease Markers

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Background. This research explores the underlying link between diagnosis and therapy between bone morphogenetic protein 1 (BMP1) and various cancers. Methods. Three immunotherapeutic cohorts, by the composition of IMvigor210, GSE35640, and GSE78220 were obtained from previously published articles and the Gene Expression Omnibus database. The different expressions of BMP1 in various clinical parameters were conducted, and prognostic analysis was executed utilizing Cox proportional hazard regression and Gene Expression Profiling Interactive Analysis. Moreover, the correlation between BMP1 and tumor microenvironment was analyzed using ESTIMATE and CIBERSORT algorithms. Tumor mutational burden and microsatellite instability were also included. The correlation between m6A modification and the gene expression level was analyzed using Tumor IMmune Estimation Resource, the University of Alabama at Birmingham Cancer data analysis portal. Gene Set Cancer Analysis analyzed the correlation of BMP1 expression level with copy number variations and methylation. Furthermore, the correlation between BMP1 and therapeutic response after antineoplastic drug use was illustrated for further discussion. Results. BMP1 expression had significant differences in 14 cancers. It presented an intimate relationship with immune-relevant biomarkers. A variation analysis indicated that BMP1 had a significant association with immunotherapeutic response. The expression level of BMP1 was closely associated with insulin-like growth factor binding protein 3, an m6A modification relative gene. Except for a few cancer types, methylation negatively correlated with BMP1, and copy number variations positively correlated with BMP1. Notably, low BMP1 expression was connected with immunotherapeutic response in the cohorts, and its expression was related to increased sectional sensitivity of drugs. Conclusion. BMP1 may serve as a potential biomarker for prognostic prediction and immunologic infiltration in diversified cancers, providing a new thought approach for oncotherapy.

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“…A study found that METTL3 induced UCK2 m6A hypermethylation and promoted the metastasis of melanoma cells through the WNT/β-catenin pathway [ 290 ]. METTL3 may be involved in the proliferation, invasion, migration and resistance of melanoma cells [ 291 , 292 ]. ALKBH5 increases the stability and expression of FOXM1 mRNA via m6A demethylation and induce the epithelial-mesenchymal transition (EMT) to promote melanoma metastasis [ 110 ].…”

Section: M6a and Cancersmentioning

confidence: 99%

Role of m6A writers, erasers and readers in cancer

Fang

Mei

et al. 2022

Exp Hematol Oncol

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The N(6)-methyladenosine (m6A) modification is the most pervasive modification of human RNAs. In recent years, an increasing number of studies have suggested that m6A likely plays important roles in cancers. Many studies have demonstrated that m6A is involved in the biological functions of cancer cells, such as proliferation, invasion, metastasis, and drug resistance. In addition, m6A is closely related to the prognosis of cancer patients. In this review, we highlight recent advances in understanding the function of m6A in various cancers. We emphasize the importance of m6A to cancer progression and look forward to describe future research directions.

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METTL3 induces PLX4032 resistance in melanoma by promoting m6A-dependent EGFR translation

Cited by 35 publications

References 39 publications

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

An Analysis of BMP1 Associated with m6A Modification and Immune Infiltration in Pancancer

Role of m6A writers, erasers and readers in cancer

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