Dysregulated N6‐methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer

Liu, T.; Yang, Sheng; Sui, Jing; Xu, Siyi; Yan-ping, Cheng; Shen, Bo; Zhang, Yan; Zhang, Xiaomei; Ye, Lihong; Pu, Yuepu; Liang, Geyu

doi:10.1002/jcp.28994

Cited by 104 publications

(92 citation statements)

References 62 publications

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“…m6A RNA modification is a hotspot in the field of regulation in recent years, involving multiple cellular processes such as mRNA maturation, protein translation and molecular structure transformation . There is growing evidence that m6A dysregulation has a profound impact on the pathogenesis of many diseases, including GC . We examined the expression of WTAP in GC samples and found that WTAP expression in tumour tissues was higher than that in adjacent tissues.…”

Section: Discussionmentioning

confidence: 99%

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

Qiao

et al. 2020

J Cellular Molecular Medi

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Background: N6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in gastric cancer (GC) tumourigenesis, providing novel insights into the molecular pathogenesis of GC.However, the involvement of Wilms' tumour 1-associated protein (WTAP), a key component of m6A methylation, in GC progression is controversial. Here, we investigated the biological role and underlying mechanism of WTAP in GC. Methods: We determined WTAP expression using tissue microarrays and The CancerGenome Atlas (TCGA) data set, which was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). CIBERSORT was used to determine WTAP expression in 22 immune cell types. Results:Wilms' tumour 1-associated protein was highly expressed in GC, which indicated a poor prognosis, and WTAP expression served as an independent predictor of GC survival. By WGCNA, GO, KEGG and core gene survival analyses, we found that high WTAP expression correlated with RNA methylation and that low expression correlated with a high T cell-related immune response. CIBERSORT was used to correlate low WTAP expression with T lymphocyte infiltration. Conclusion: RNA methylation and lymphocyte infiltration are the main causes of high WTAP expression and poor prognosis, respectively. K E Y W O R D S differentially expressed genes, DNA methylation, gastric cancer, N6-methyladenosine (m6A) methylation, WTAP | 4453 LI et aL.

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Section: Discussionmentioning

confidence: 99%

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

Qiao

et al. 2020

J Cellular Molecular Medi

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“…Conversely, METTL3 can promote pri-miRNA processing by interacting with DGCR8 (2,20,54). Dysregulation of METTL3 in various cancers can also influence cancer cell EMT (23,49,50), apoptosis (36,47), and stem cell self-renewal (38,39), which have been identified to be important in cancer progression. In addition, METTL3-mediated m 6 A modification can directly regulate the transcription and translation of oncogenes and tumor suppressors coupled to the most of the important pathways involved in cancer cell progression, such as the PI3K/AKT (36,44,47,57,60,62), wnt/βcatenin (46), and P38/ERK (26) pathways.…”

Section: Discussion and Outlookmentioning

confidence: 99%

“…METTL3 and m 6 A were upregulated in human osteosarcoma (46), gastric cancer (23,47,48), melanoma (49), ovarian carcinoma (50), and hepatocellular carcinoma (51). Its expression level gradually increased with the increasing tumor stage and grade.…”

Section: Mettl3 In Other Cancersmentioning

confidence: 95%

“…Zhou et al showed that METTL3 and METTL14 exhibited higher expression in clear cell renal cell carcinoma than in normal samples and that patients with deletion of METTL3 had poorer overall survival (OS) and disease-free survival (DFS) (22). Liu et al revealed that the proliferation, viability, and migration of gastric cancer cells with METTL3 silencing in vitro were significantly inhibited compared with those of control cells (23). This research group also noted that METTL3 expression was associated with biological processes, including adipogenesis, the mTOR pathway, and reactive oxygen species (24).…”

Section: Introductionmentioning

confidence: 99%

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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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“…The METTL3 RNA methyltransferase is a "writer" protein responsible for m 6 A modification and is involved in mRNA biogenesis, decay, and translation. METTL3 may play a carcinogenic role in lung cancer [39], bladder cancer [23,40], gastric cancer [41], osteosarcoma [42], cutaneous squamous cell carcinoma [43], and acute myeloid leukemia (AML) [44]. Li et al [45] reported that METTL3 promoted colorectal cancer progression through an m 6 A-IGF2BP2dependent mechanism, while Deng et al [46] reported that METTL3 inhibited the proliferation and migration of colorectal cancer cells through the p38/ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

Qin

Zhang

et al. 2020

BMC Cancer

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Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators ("writer," "eraser," and "reader" proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

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Dysregulated N6‐methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer

Cited by 104 publications

References 62 publications

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

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

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

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