The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network

Cheng, Maosheng; Lü, Sheng; Gao, Qian; Xiong, Qing; Zhang, Haojie; Wu, Mingqing; Yu, Liang; Zhu, Fengyu; Zhang, Yingyin; Zhang, Xiuhong; Yuan, Quan; Li, Yang

doi:10.1038/s41388-019-0683-z

Cited by 326 publications

(288 citation statements)

References 65 publications

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“…However, METTL3 has recently been reported to play crucial roles through m6A epitranscriptional modification in several common cancers. 43,44 Whether METTL3 affects the progression of HB through a m6A modification pattern remains a subject for further study.…”

Section: Mettl3mentioning

confidence: 99%

Cross talk between RNA N6‐methyladenosine methyltransferase‐like 3 and miR‐186 regulates hepatoblastoma progression through Wnt/β‐catenin signalling pathway

Cui

Wang

et al. 2020

Cell Proliferation

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Objectives N6‐methyladenosine (m6A) is a ubiquitous epigenetic RNA modification that plays a pivotal role in tumour development and metastasis. In this study, we aimed to investigate the expression profiling, clinical significance, biological function and the regulation of m6A‐related genes in hepatoblastoma (HB). Materials and Methods The mRNA and protein expression levels of m6A‐related genes were analysed using Gene Expression Omnibus (GEO) and tissue microarray (TMA) cohort. Kaplan‐Meier analysis was performed to evaluate the prognostic value of m6A‐related genes in HB. Knockdown of m6A‐related genes was conducted to analyse its function on cell proliferation, migration and invasion. Furthermore, bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. Results We found that most m6A‐related genes were significantly upregulated in HB tumour tissues. High levels of methyltransferase‐like 3 (METTL3, P = .013), YTHDF2 (P = .037) and FTO (P = .032) indicated poor clinical outcomes, and the upregulation of METTL3 was an independent prognostic factor in HB patients. Functional assays showed that knockdown of METTL3 could dramatically suppress the proliferation, migration and invasion of HB cells. In addition, METTL3 was identified to be a direct target of microRNA‐186 (miR‐186). Consistently, miR‐186 was low expressed in HB tumour tissues. Moreover, overexpression of miR‐186 significantly inhibited cell aggressive phenotype both in vitro and in vivo, while the inhibitory effect could be reversed by METTL3 overexpression. Mechanism study indicated that miR‐186/METTL3 axis contributed to the progression of HB via the Wnt/β‐catenin signalling pathway. Conclusions M6A‐related genes were frequently dysregulated in HB. miR‐186/METTL3/Wnt/β‐catenin axis might serve as novel therapeutic targets and prognostic biomarkers in HB.

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Section: Mettl3mentioning

confidence: 99%

Cross talk between RNA N6‐methyladenosine methyltransferase‐like 3 and miR‐186 regulates hepatoblastoma progression through Wnt/β‐catenin signalling pathway

Cui

Wang

et al. 2020

Cell Proliferation

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“…Recent studies noted that METTL3 was drastically upregulated in bladder cancer tissues and was related to tumor histological grade. Patients with high expression of METTL3 had poor prognosis and reduced survival time (28)(29)(30). Knockdown of METTL3 significantly reduced bladder cancer cell invasion, proliferation, and survival in vitro and tumorigenicity in vivo (31).…”

Section: Mettl3 In Urological Tumorsmentioning

confidence: 99%

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N 6 -methyladenosine (m 6 A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro-or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m 6 A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

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“…23 Recent studies showed that m6A modification played essential roles in tissue development, stem cell formation and differentiation, 24,25 control of heat shock response 26 and circadian clock controlling, 27 as well as in tumours formation. [28][29][30][31][32][33][34][35] As the critical m6A methyltransferase, the role of METTL3 in tumours is controversial.…”

Section: Introductionmentioning

confidence: 99%

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

Zhu

et al. 2020

J Cellular Molecular Medi

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m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6‐methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′‐untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down‐regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner, representing a promising therapeutic strategy for the treatment of CRC.

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The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network

Cited by 326 publications

References 65 publications

Cross talk between RNA N6‐methyladenosine methyltransferase‐like 3 and miR‐186 regulates hepatoblastoma progression through Wnt/β‐catenin signalling pathway

Cross talk between RNA N6‐methyladenosine methyltransferase‐like 3 and miR‐186 regulates hepatoblastoma progression through Wnt/β‐catenin signalling pathway

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

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