Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer

Wang, Xiuli; Li, Zenghui; Kong, Beihua; Song, Chen; Cong, Jianglin; Hou, Jianquan; Wang, Shaoguang

doi:10.18632/oncotarget.22041

Cited by 81 publications

(75 citation statements)

References 32 publications

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“…Consistently, it was observed that m 6 A obtained low expression in cervical cancer, and the reduced m 6 A level was associated with higher FIGO stage and recurrence. 45 Further investigation showed that down-regulation of m 6 A level induced by interference of METTL3 and METTL14 or overexpression of FTO and ALKBH5 could promote cervical cell proliferation, and vice versa. Herein, we conclude the possible mechanisms about m 6 A-associated proteins in other cancers as follows.…”

Section: A Modification Inhibits the Tumour Progressionmentioning

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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Section: A Modification Inhibits the Tumour Progressionmentioning

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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“…[4][5][6][7] Recent literatures have validated the correlation between m6A and human cancers including hepatocellular carcinoma, breast cancer, pancreatic cancer and cervical cancer. [8][9][10][11] However, the clinical values and biological roles of m6A-related genes in HB have not been reported. METTL3 is an RNA methyltransferase that can modify the biological occurrence, decay and translation control of mRNA by m6A.…”

Section: Introductionmentioning

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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“…The potential involvement of m 6 A in cancer is reinforced by the enriched proteoglycans in cancer KEEG pathway (22 genes, PBenjamini = 2.43╳10 -2 ). This is not surprising as there is increasing evidence demonstrating its regulatory roles in different cance r [20,[64][65][66][67][68][69][70]. Another enriched KEGG pathways are Protein processing in the endoplasmic reticulum (20 genes, PBenjamini = 2.37╳10 -2 ) and Lysosome pathway (18 genes, PBenjamini = 6.31╳10 -3 ), both of which are protein processing pathways.…”

Section: Functional Significant M 6 A-regulated Genes Identified By Hmentioning

confidence: 96%

Global analysis of N6-methyladenosine functions and its disease association using deep learning and network-based methods

Zhang

Fan

et al. 2018

Preprint

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N6-methyladenosine (m 6 A) is the most abundant methylation, existing in >25% of human mRNAs. Exciting recent discoveries indicate the close involvement of m 6 A in regulating many different aspects of mRNA metabolism and diseases like cancer. However, our current knowledge about how m 6 A levels are controlled and whether and how regulation of m 6 A levels of a specific gene can play a role in cancer and other diseases is mostly elusive. We propose in this paper a computational scheme for predicting m 6 A-regulated genes and m 6 A-associated disease, which includes Deep-m 6 A, the first model for detecting condition-specific m 6 A sites from MeRIP-Seq data with a single base resolution using deep learning and a new network-based pipeline that prioritizes functional significant m 6 A genes and its associated diseases using the Protein-Protein Interaction (PPI) and gene-disease heterogeneous networks. We applied Deep-m 6 A and this pipeline to 75 MeRIP-seq human samples, which produced a compact set of 709 functionally significant m 6 A-regulated genes and nine functionally enriched subnetworks. The functional enrichment analysis of these genes and networks reveal that m 6 A targets key genes of many critical biological processes including transcription, cell organization and transport, and cell proliferation and cancer-related pathways such as Wnt pathway.The m 6 A-associated disease analysis prioritized five significantly associated diseases including leukemia and renal cell carcinoma. These results demonstrate the power of our proposed computational scheme and provide new leads for understanding m 6 A regulatory functions and its roles in diseases.Keywords: N6-methyladenosine (m 6 A), methylated RNA immunoprecipitation sequencing (MeRIP-Seq ), convolutional neural networks, m 6 A site prediction, m 6 A functional prediction, m 6 A-disease association Author summaryThe goal of this work is to identify functional significant m 6 A-regulated genes and m 6 A-associated diseases from analyzing an extensive collection of MeRIP-seq data. To achieve this, we first developed Deep-m 6 A, a CNN model for single-base m 6 A prediction. To our knowledge, this is the first condition-specific single-base m 6 A site prediction model that combines mRNA sequence feature and MeRIP-Seq data. The 10-fold cross-validation and test on an independent dataset show that Deep-m 6 A outperformed two sequence-based models. We applied Deep-m 6 A followed by network-based analysis using HotNet2 and RWRH to 75 human MeRIP-Seq samples from various cells and tissue under different conditions to globally detect m 6 A-regulated genes and further predict m 6 A mediated functions and associated diseases. This is also to our knowledge the first attempt to predict m 6 A functions and associated diseases using only computational methods in a global manner on a large number of human MeRIP-Seq samples. The predicted functions and diseases show considerable consistent with those reported in the literature, which demonstrated the power of our proposed pipe...

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Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer

Cited by 81 publications

References 32 publications

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

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

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

Global analysis of N6-methyladenosine functions and its disease association using deep learning and network-based methods

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