Recent advances of m6A methylation modification in esophageal squamous cell carcinoma

Zhang, Xiaoqing; Lü, Ning; Wang, Li; Wang, Yixuan; Li, Minna; Zhou, Ying; Cui, Manli; Zhang, Mingxin; Zhang, Lingmin

doi:10.1186/s12935-021-02132-2

Cited by 20 publications

(15 citation statements)

References 65 publications

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“…Li J showed that in the pathophysiology of ESCC, ALKBH5 acts as a tumor suppressor ( Li et al, 2021 ). Due to advances in biological technologies such as high-throughput sequencing and the discovery of abnormal expression of METTL3, ALKBH5, and FTO, the role of m 6 A methylation in ESCC has gradually been revealed ( Zhang et al, 2021 ). The insidious onset of ESCC is primarily responsible for the patients’ poor prognosis, and by the time of diagnosis, the majority had advanced to the middle and late stages of lymphatic metastasis.…”

Section: Discussionmentioning

confidence: 99%

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma

et al. 2022

Front. Pharmacol.

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Epigenetic regulation plays a critical role in the development, progression, and treatment of tumors. The most common chemical modification of mRNA, called m6A, is essential for controlling mRNA stability, splicing, and translation. Methyltransferase-like 3 (METTL3) is an important m6A methyltransferase. The mechanism of action of METTL3 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this investigation, we sought to clarify the function and clinical importance of METTL3 in ESCC and investigate its underlying mechanisms. We discovered that METTL3 has a significant proliferative effect in ESCC cells by using lentiviral construction of stable cell lines overexpressing METTL3 (METTL3-OE) and knocking down METTL3 (sh-METTL3). To create a xenograft tumor model, we inoculated KYSE510 cells subcutaneously into BALB/c nude mice and discovered that sh-METTL3 inhibited the tumorigenicity of esophageal cancer KYSE510 cells in the nude mouse tumor model. MeRIP-seq and RNA-seq analysis revealed IFIT2 to be a METTL3 target gene. The findings revealed that METTL3 regulates IFIT2 and thus influences malignant biological behaviors such as proliferation, migration, and invasion of ESCC, as well as the immune microenvironment of tumors.

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Section: Discussionmentioning

confidence: 99%

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma

et al. 2022

Front. Pharmacol.

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“…N6-methyladenosine (m6A) is the most common epigenetic RNA modification that plays an important role in the regulation of malignancies ( 2 ). Despite the potential of m6A for the diagnosis and treatment of ESCA ( 3 , 4 ), its potential targets and mechanisms remain unclear.…”

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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“…Currently identified m6A ‘readers’ include YTH domain family members (YTHDC1, YTHDC2, YTHDF1, YTHDF2 and YTHDF3), heterogeneous nuclear ribonucleoprotein (HNRNP) family members (HNRNPC and HNRNPA2B1), insulin-like growth factor 2 mRNA-binding proteins (IGF2BP1, IGF2BP2 and IGF2BP3), fragile X mental retardation 1 (FMR1) and leucine rich pentatricopeptide repeat containing (LRPPRC) [ 48 , 64 ]. These ‘readers’ possess the ability to recognize m6A modifications in RNAs and generate functional signals [ 65 ].…”

Section: Molecular Basis For M6a Modificationmentioning

confidence: 99%

“…Stable complexes are the main gateway to epigenetic methylation machinery. In addition to the KIAA1429/WTAP complex, one known complex of m6A methyltransferases consists of WTAP, METTL3 and METTL14 [ 53 , 64 ]. Although it forms a protein complex to coordinate with WTAP/METTL14 in m6A modification, METTL3 seems at be the core of this process in endometrioid EOC, stemming from the fact that knockdown of METTL3, but not WTAP/METTL14, decreased the m6A levels of associated targets (determined in vitro by RIP-qPCR) [ 76 ].…”

Section: Biological Functions Of M6a Related Regulators In Ovarian Cancermentioning

confidence: 99%

Emerging role of m6A methylation modification in ovarian cancer

Chang

Liu

et al. 2021

Cancer Cell Int

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Abstractm6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC. Graphical Abstract

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Recent advances of m6A methylation modification in esophageal squamous cell carcinoma

Cited by 20 publications

References 65 publications

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma

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

Emerging role of m6A methylation modification in ovarian cancer

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