YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway

Shen, Xudong; Zhao, Kui; Xu, Liming; Cheng, Guangfeng; Zhu, Jian-Hong; Gan, Lei; Wu, Yongyou; Zhuang, Zhixiang

doi:10.3389/fgene.2020.592042

Cited by 37 publications

(34 citation statements)

References 28 publications

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“…YTHDF1 and its m 6 A-mediated regulation of Wnt/β-catenin signaling promote gastric cancer progression. METTL3-mediated m 6 A modification facilitates gastric cancer progression and has poor prognosis ( Pi et al, 2020 ; Shen et al, 2020 ; Wang Q. et al, 2020 ). Also, HNRNPC and YTHDF1 have an effect on prognosis in breast cancer patients ( Wu et al, 2018 ; Anita et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Immune Infiltrates and PD-L1 of m6A RNA Methylation Regulators in Hepatocellular Carcinoma

Deng

et al. 2021

Front. Cell Dev. Biol.

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Recently, N6-methyladenosine (m6A) RNA methylation in eukaryotic mRNA has become increasingly obvious in the pathogenesis and prognosis of cancer. Moreover, tumor microenvironment is involved in the regulation of tumorigenesis. In our research, the clinical data, including 374 tumor and 50 normal patients, were obtained from The Cancer Genome Atlas (TCGA). Then 19 m6A regulators were selected from other studies. Hepatocellular carcinoma (HCC) patients were clustered in cluster1/2, according to the consensus clustering for the m6A RNA regulators. We found that m6A regulators were upregulated in cluster1. The cluster1 was associated with higher programmed death ligand 1 (PD-L1) expression level, higher immunoscore, worse prognosis, and distinct immune cell infiltration compared with cluster2. Five risk signatures were identified, including YTH N6-methyladenosine RNA-binding protein 1, YTHDF2, heterogeneous nuclear ribonucleoprotein C, WT1-associated protein, and methyltransferase-like 3, based on univariate Cox and least absolute shrinkage and selection operator regression analysis. High-risk group and low-risk group HCC patients were selected based on the risk score. Similarly, the high-risk group was extremely associated with higher PD-L1 expression level, higher grade, and worse overall survival (OS). Also, cluster1 was mainly enriched in high-risk group. Receiver operating characteristic (ROC) and a nomogram were used to predict the ability and the probability of 3- and 5-year OS of HCC patients. The time-dependent ROC curve (AUC) reached 0.77, 0.67, and 0.68 at 1, 3, and 5 years in the training dataset. Also, AUC areas of 1, 3, and 5 years were 0.7, 0.63, and 0.55 in the validation dataset. The gene set enrichment analysis showed that MTOR signaling pathway and WNT signaling pathway were correlated with cluster1 and high-risk group. Collectively, the research showed that the m6A regulators were significantly associated with tumor immune microenvironment in HCC. Risk characteristics based on m6A regulators may predict prognosis in patients with HCC and provide a new therapeutic target for improving the efficacy of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Immune Infiltrates and PD-L1 of m6A RNA Methylation Regulators in Hepatocellular Carcinoma

Deng

et al. 2021

Front. Cell Dev. Biol.

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“…YTHDF2 binding to m 6 A promotes RNA decay, while YTHDC2 is involved in mRNA degradation and translation initiation. These regulators were demonstrated to play a crucial role in a variety types of cancers [ 21 , 30 , 31 , 32 ]. The role of the YTHDF2 gene in HNSCC has not been explored so far, whereas YTHDC2 was found to be a tumor suppressor with low expression in HNSCC samples, while its upregulation was associated with longer-term survival and the recurrence-free survival of HNSCC patients [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients

et al. 2021

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RNA methylation at the nitrogen sixth of adenosine (m6A, N6-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m6A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m6A modification by the mass spectrometry approach and determine the mRNA expression level of selected m6A RNA methyltransferase (METTL3), demethylase (FTO), and m6A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m6A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m6A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m6A differences between cancerous and histopathologically unchanged tissues suggests that m6A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis.

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“…In addition, YTHDF2 is down-regulated in gastric cancer tissues and cells. Overexpression of YTHDF2 significantly inhibited the proliferation, invasion and migration of gastric cancer cells by negatively regulating forkhead box C2 (FOXC2), which acts as an oncogene in various cancers such as nasopharyngeal cancer, colorectal cancer and triple negative breast cancer (71,(83)(84)(85).…”

Section: Gastric Cancermentioning

confidence: 99%

Main N6-Methyladenosine Readers: YTH Family Proteins in Cancers

Dai

Shi

et al. 2021

Front. Oncol.

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Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by “writers,” consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by “erasers,” including FTO and ALKBH5. Moreover, m6A modification is recognized by “readers,” which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.

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YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway

Cited by 37 publications

References 28 publications

Comprehensive Analysis of the Immune Infiltrates and PD-L1 of m6A RNA Methylation Regulators in Hepatocellular Carcinoma

Comprehensive Analysis of the Immune Infiltrates and PD-L1 of m6A RNA Methylation Regulators in Hepatocellular Carcinoma

The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients

Main N6-Methyladenosine Readers: YTH Family Proteins in Cancers

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