HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g

Cai, Xiaoli; Xiao, Wenqin; Cao, Can; Gao, Yuen; Zhang, Shuqin; Yang, Zhe; Liu, Yunxia; Zhang, Xiaodong; Zhang, Weiying; Ye, Lihong

doi:10.1016/j.canlet.2017.11.018

Cited by 390 publications

(348 citation statements)

References 47 publications

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“…31 Cai X et al also showed that METTL3 promoted the progression of breast cancer by inhibiting tumour suppressor let-7g. 32 In summary, our study robustly demonstrated that METTL3 was significantly upregulated and functioned as an oncogene in human HB.…”

Section: Discussionsupporting

confidence: 58%

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: Discussionsupporting

confidence: 58%

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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“…In the meanwhile, METTL3 promoted the expression of HBXIP by m 6 A modification. Thus, an HBXIP/let‐7 g/METTL3‐positive feedback loop forms, leading to the proliferation of breast cancer cells 91. Apart from the above, there are more encouraging findings associated with AML.…”

Section: The Dual Role Of M6a Modification In Human Cancersmentioning

confidence: 98%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

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As the most abundant and reversible RNA modification in eukaryotic cells, m6A triggers a new layer of epi‐transcription. M6A modification occurs through a methylation process modified by “writers” complexes, reversed by “erasers”, and exerts its role depending on various “readers”. Emerging evidence shows that there is a strong association between m6A and human diseases, especially cancers. Herein, we review bi‐aspects of m6A in regulating cancers mediated by the m6A‐associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6A‐targeted therapies including competitive antagonists of m6A‐associated proteins may provide a new tumour intervention in the future.

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“…The METTL3-induced m 6 A mark also drives malignant progression in breast tumor in aid of hepatitis B X-interacting protein (HBXIP), an oncogene in breast cancer cells (45).…”

Section: Mettl3mentioning

confidence: 99%

N6-Methyladenosine: A Novel RNA Imprint in Human Cancer

Liu

et al. 2019

Front. Oncol.

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N 6 -Methyladenosine (m 6 A), a pervasive posttranscriptional modification which is reversible, has been among hotspot issues in the past several years. The balance of intracellular m 6 A levels is dynamically maintained by methyltransferase complex and demethylases. Meanwhile, m 6 A reader proteins specifically recognize modified residues and convey messages so as to set up an efficient and orderly network of m 6 A regulation. The m 6 A mark has proved to affect every step of RNA life cycle, from processing in nucleus to translation or degradation in cytoplasm. Subsequently, disorders in m 6 A methylation are directly related to aberrant RNA metabolism, which results in tumorigenesis and altered drug response. Therefore, uncovering the underlying mechanism of m 6 A in oncogenic transformation and tumor progression seeks opportunities for novel targets in cancer therapy. In this review, we conclude the extensive impact of m 6 A on RNA metabolism and highlight its relevance with human cancer, implicating the far-reaching value in clinical application.

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HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g

Cited by 390 publications

References 47 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

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

N6-Methyladenosine: A Novel RNA Imprint in Human Cancer

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