METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway

Hou, Huaying; Zhao, Huidong; Yu, Xiaoming; Cong, Ping; Zhou, Yong; Jiang, Yuhua; Cheng, Yufeng

doi:10.1016/j.prp.2020.153087

Cited by 31 publications

(30 citation statements)

References 24 publications

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“…Over the past decades, the roles of m6A regulators in EC had been revealed in several previous studies. For example, METTL3 enhanced the progression of EC cells through the Akt signaling pathway (Hou et al, 2020). The up-regulation of METTL3 expression indicates a poor prognosis in patients with ESCC.…”

Section: Discussionmentioning

confidence: 98%

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Zhao

Xie

et al. 2021

Front. Cell Dev. Biol.

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N6 methyladenosine (m6A) RNA methylation regulators play an important role in the development of tumors. However, their function in esophageal cancer (EC) has not been fully elucidated. Here, we analyzed the gene expression data of 24 major m6A RNA methylation regulators from 775 patients with EC from TCGA dataset. The present study showed the aberrations of m6A regulators in genome were correlated to prognosis in human ECs. Meanwhile, 17 m6A regulators showed increased expression in EC samples, including YTHDC1, IGF2BP2, FTO, METTL14, YTHDF3, RBM15, WTAP, HNRNPA2B1, HNRNPC, ALKBH5, YTHDF2, METTL16, IGF2BP3, VIRMA, RBM15B, YTHDF1, KIAA1429, HAKAI, and ZC3H13. Among them, we found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC. Furthermore, we showed levels of m6A regulators is correlated with the expression of Immuno-regulators (Immunoinhibitors, Immunostimulators, and MHC molecules) and immune infiltration levels in EC. Bioinformatics further confirm m6A regulators were involved in regulating RNA splicing, RNA stability, and cell proliferation. Our study showed m6A regulators are promising targets and biomarkers for cancer immunotherapy in EC.

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Section: Discussionmentioning

confidence: 98%

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Zhao

Xie

et al. 2021

Front. Cell Dev. Biol.

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“…YTHDF1 ("Reader" proteins of m6A modi cation) can promote the occurrence and metastasis of ovarian cancer by binding with E6A modi ed EIF3C mRNA, and the up regulation of YTHDF1 is associated with poor prognosis of ovarian cancer patients [50] . Another study showed that METTL3 plays a carcinogenic role partly through AkT signaling pathway in the process of esophageal cancer, which indicates that METTL3 can be used as a potential therapeutic target for esophageal cancer treatment [51] . Thus, the above results demonstrated that m6A modi cation often depends on the related protein signaling pathway to abnormal expression of targeted genes, to participating in the proliferation, apoptosis and metastasis of cancer.Herein,t he purpose of our study is to identify the differentially expressed genes(DEGs) modi ed by m6A in OC and investigate the protein pathway that the modi cation depends on.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis: Screening and Identification of Differentially Expressed Genes Modified by m6A in Ovarian Cancer

Liu

Zhang

Lou

2020

Preprint

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Background: N6-methyladenosine(m6A) is one of the most common RNA modifications that occurs at the nitrogen-6 position of adenine. Emerging evidence has revealed that regulatory functions of m6A play an essential role in the development of cancer. However the study of m6A in ovarian cancer(OC) is still in our infancy. In this work ,we aimed to identify and analysis the differentially expressed genes(DEGs） modified by m6A which can provide new therapeutic targets and key biomarkers in OC.Methods: We downloaded Microarray datasets GSE146553 and GSE124766 from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by GEO2R analysis tools. Subsequently, The DAVID database was used to construct Enrichment analysis of GO and KEGG pathways. Next, the DEGs modified by m6A were identified by m6AVar database. Finally, the functional analysis and clinical sample validation of these genes were verified by ONCOMINE, GEPIA, cBioPortal online platform and Kaplan-Meier Plotter.Results:152 DEGs were selected ,and the DEGs were mainly enriched in extracellular exosome, spindle microtubule, response to hypoxia and cell cycle .And we identified 15 DEGs which were modified by m6A:MAPK10、MXRA5、CHD7、MECOM、SCN7A、GREB、PRUNE2、MX2、TOP2A、JAM2、DST、LAPTM5、CDKN2A、GATM and ANGPTL1. After statistical analysis, two DEGs (SCN7A and GAMT) were selected for detailed study. We revealed that SCN7A and GAMT were expressed at a low level in OC. Afterwards, Survival analysis showed that SCN7A and GAMT expression were correlated with OC overall survival. And the expression of SCN7A and GAMT mRNA decreasing in different TNM stages. Finally, we presumed that the modification of m6A spongs GAMT via EIF4A3 or FUS to participate in the occcurrence and the development of OC.Conclusion: Altogether, the current study identified and analysised the DEGs modified by m6A in OC. It will help us to investigate the underlying mechanism and progression of OC. In addition, it can provide new diagnostic markers and potential therapeutic targets in OC.

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“…METTL3 has been shown to be upregulated in ESCC tissues and correlate with worse prognosis [ 91 , 92 , 93 ]. The inhibition of METTL3 inhibited the proliferation in esophageal cancer cell lines via inhibition of AKT signaling [ 87 ]. One recent study found that variants in the YTHDC2 gene were associated with ESCC risk, and that knocking down YTHDC2 impaired the proliferation rate of ESCC cells [ 88 ].…”

Section: The Mettl3-m 6 a Epitranscriptome: Key Player In Epithelial Cancersmentioning

confidence: 99%

The METTL3-m6A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer

López

Capell

2021

Genes

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Dynamic modifications on RNA, frequently termed both, “RNA epigenetics” and “epitranscriptomics”, offer one of the most exciting emerging areas of gene regulation and biomedicine. Similar to chromatin-based epigenetic mechanisms, writers, readers, and erasers regulate both the presence and interpretation of these modifications, thereby adding further nuance to the control of gene expression. In particular, the most abundant modification on mRNAs, N6-methyladenosine (m6A), catalyzed by methyltransferase-like 3 (METTL3) has been shown to play a critical role in self-renewing somatic epithelia, fine-tuning the balance between development, differentiation, and cancer, particularly in the case of squamous cell carcinomas (SCCs), which in aggregate, outnumber all other human cancers. Along with the development of targeted inhibitors of epitranscriptomic modulators (e.g., METTL3) now entering clinical trials, the field holds significant promise for treating these abundant cancers. Here, we present the most current summary of this work, while also highlighting the therapeutic potential of these discoveries.

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METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway

Cited by 31 publications

References 24 publications

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Bioinformatic Analysis: Screening and Identification of Differentially Expressed Genes Modified by m6A in Ovarian Cancer

The METTL3-m6A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer

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METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway

Cited by 31 publications

References 24 publications

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Bioinformatic Analysis: Screening and Identification of Differentially Expressed Genes&nbsp;Modified by m6A&nbsp;in Ovarian Cancer

The METTL3-m6A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer

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Bioinformatic Analysis: Screening and Identification of Differentially Expressed Genes Modified by m6A in Ovarian Cancer