METTL3-mediated m6A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway

Han, Hui; Yang, Chunlong; Zhang, Shuishen; Cheng, Maosheng; Guo, Siyao; Zhu, Yan; Ma, Jiachi; Yu, Liang; Wang, Lu; Zheng, Siyi; Wang, Zhaoyu; Chen, Demeng; Jiang, Yi‐Zhou; Lin, Shuibin

doi:10.1016/j.omtn.2021.07.007

Cited by 44 publications

(38 citation statements)

References 32 publications

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“…Another study showed that FTO is involved in oncogenesis of ESCA through upregulation of MMP13 ( 9 ). In addition, METTL3 may also promote ESCA proliferation and invasion by regulating multiple pathways, such as AKT ( 10 ), Notch ( 11 ), COL12A1/MAPK ( 12 ) and other signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Identification of clinical prognostic features of esophageal cancer based on m6A regulators

et al. 2022

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BackgroundEsophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA.MethodsRNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsIn ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

Identification of clinical prognostic features of esophageal cancer based on m6A regulators

et al. 2022

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“…Studies have found that the m6A regulators in esophageal cancer all play a cancer-promoting role, except for ALKBH5 [ 100 , 256 ]. The downstream targets that the m6A writer METTL3 regulates in esophageal cancer are GLS2 [ 257 ], p21 [ 258 ], Wnt/β-catenin [ 38 , 259 ], AKT [ 259 ], the EMT [ 259 ], and the Notch [ 260 ] signaling pathway. ALKBH5 plays dual roles in promoting and suppressing tumor growth in esophageal cancer.…”

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 in human tissue is highly expressed and conserved, especially in the testes. Recent studies reported that METTL3 is significantly highly expressed in chronic myeloid leukemia ( Ianniello et al, 2021 ), thymic epithelial tumors ( Iaiza et al, 2021 ), esophageal cancer ( Han et al, 2021 ), and prostate cancer ( Chen et al, 2021b ), suggesting a close relationship with malignant tumor development. Previous studies also suggested that METTL3 is significantly up-regulated in BC.…”

Section: M6a Roles and Mechanisms In Bcmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

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METTL3-mediated m6A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway

Cited by 44 publications

References 32 publications

Identification of clinical prognostic features of esophageal cancer based on m6A regulators

Identification of clinical prognostic features of esophageal cancer based on m6A regulators

Role of m6A writers, erasers and readers in cancer

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

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