m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer

Wang, Yanyun; Li, Man; Chen, Yitong; Zhang, Shoudan

doi:10.1016/j.omto.2021.04.011

Cited by 38 publications

(26 citation statements)

References 28 publications

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“…What's more, with population of studies in m6A, they were also found in prostate cancer 34 , renal cancer 35,36 , bladder carcinoma 37 , gastric cancer 38 , liver cancer 39 , and lung cancer 40 . However, what the role they played in SGCT in testicles were still unknown.…”

Section: Discussionmentioning

confidence: 92%

A risk prediction model Construction as an Independent Disease-Free Prognostic Indicator for Seminoma by Bioinformatic Analysis

Chen

Zhifeng

2022

Preprint

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Background N6-Methyladenosine (m6A) are significant in directing different genes’ expression and their phenotype in different types of cancers. On the other hand, the function of m6A in seminomatous germ cell tumors (SGCT) is still unexplored. Our research attempts to demonstrate the disease-free prognosis value of m6A RNA methylation regulators in SGCT. Methods The gene expression and accompanying clinical data of 65 SGCT tissues and 85 NSGCT tissues retrieved from the TCGA database were analyzed. A series of R packages were applied for our study. Results The landscape of m6A RNA methylation regulators in SGCT was displayed. All SGCT patients were grouped into two clusters by consensus clustering of m6A RNA methylation regulators, and the clusters were connected to the disease-free prognosis and clinicopathological characteristics of SGCT(p = 0.015). Furthermore, the risk score(1.52YTHDC1 + 2.22HNRNPC-2.735WTAP) model was obtained and constructed by the univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO) Cox regression. The risk score was interrelated with stage status and laterality status of SGCT. Under the same conditions, the right side may have a higher risk score than the left one. More significantly, the risk score can serve as an self-supporting disease-free prognostic marker for SGCT patients. Conclusions m6A RNA methylation regulators played an important role of SGCT in its disease-free survival prognosis.

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Section: Discussionmentioning

confidence: 92%

A risk prediction model Construction as an Independent Disease-Free Prognostic Indicator for Seminoma by Bioinformatic Analysis

Chen

Zhifeng

2022

Preprint

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“… 18 Wang et al recently reported that E2F1, by activating the transcription of NELL2 gene, could enhance the migration, viability, and invasion of non-small cell lung cancer (NSCLC) cells as well as influence tumor progression and metastasis of NSCLC. 19 E2F2 could promote the lung cancer cell proliferation and invasion through Lnc-NNT-AS1/miR-3666/E2F2 axis. 20 Miao et al 21 reported that the expression of E2F2 could be regulated by transcription factor FLI1, the decrease of E2F2 resulted in arrest of lung cancer cell cycle and inhibition of lung cancer proliferation.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the E2F Transcription Factor Family in Human Lung Adenocarcinoma

Wang¹,

Liu²,

Cheang³

et al. 2022

IJGM

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Background E2F transcription factors (E2Fs), code a family of pivotal transcription factors, have been identified as key regulators in tumor tumorigenesis. However, the function of E2F family in human lung adenocarcinoma (LUAD) have not been fully elucidated. Methods Herein, The Cancer Genome Atlas (TCGA) databases, Kaplan-Meier plotter, cBioPortal and TIMER were used to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of E2Fs in LUAD patients. Results The expression levels of E2Fs ( E2F1-8 ) were all significantly upregulated in LUAD tissues compared with normal lung tissues. All eight E2Fs had low rates of gene mutation in LUAD patients from cBioPortal databases. Survival analysis revealed that E2F2 (P=0.038; HR 1.36; 95% CI 1.02–1.81), E2F7 (P<0.001; HR 1.78; 95% CI 1.33–2.39) and E2F8 (P=0.03; HR 1.37; 95% CI 1.02–1.82) were significantly associated with poor prognosis. Multivariate cox regression analysis found that only E2F7 (P<0.001; HR 2.72; 95% CI 1.75–4.25) was an independent prognostic predictor in LUAD after adjusting common clinical parameters. The receiver operating characteristic (ROC) analysis also found that E2F7 had high diagnostic value for LUAD (AUC=0.901). Further analysis found that E2F7 was significantly associated with LUAD immune cell infiltration of B cell, T cell, neutrophil, and myeloid dendritic cell. E2F7 also have positive correlations with immune checkpoint genes including SIGLEC15, CD274, HAVCR2, PDCD1LG2, CTLA4, TIGIT, LAG3 and PDCD1 in LUAD. Conclusion Our findings showed various association of E2F7 in LUAD diagnostic and prognostic aspects, which suggested its potential in becoming a novel biomarker.

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“…In lung cancer, FTO overexpression promotes cell growth, migration and metastasis, in an E2F1-dependent manner. Concomitantly, the level of m 6 A level in E2F1 mRNA is reduced upon FTO overexpression, suggesting that FTO’s function in lung cancer depends on its m 6 A demethylase activity 70 . Moreover, FTO mediated m 6 A demethylation is oncogenic in OSCC.…”

Section: ‘Context-dependent’ Function Of Fto In Cancermentioning

confidence: 99%

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

2022

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The last decade has seen mRNA modification emerge as a new layer of gene expression regulation. The Fat mass and obesity-associated protein (FTO) was the first identified eraser of N6-methyladenosine (m6A) adducts, the most widespread modification in eukaryotic messenger RNA. This discovery, of a reversible and dynamic RNA modification, aided by recent technological advances in RNA mass spectrometry and sequencing has led to the birth of the field of epitranscriptomics. FTO crystallized much of the attention of epitranscriptomics researchers and resulted in the publication of numerous, yet contradictory, studies describing the regulatory role of FTO in gene expression and central biological processes. These incongruities may be explained by a wide spectrum of FTO substrates and RNA sequence preferences: FTO binds multiple RNA species (mRNA, snRNA and tRNA) and can demethylate internal m6A in mRNA and snRNA, N6,2′-O-dimethyladenosine (m6Am) adjacent to the mRNA cap, and N1-methyladenosine (m1A) in tRNA. Here, we review current knowledge related to FTO function in healthy and cancer cells. In particular, we emphasize the divergent role(s) attributed to FTO in different tissues and subcellular and molecular contexts.

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m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer

Cited by 38 publications

References 28 publications

A risk prediction model Construction as an Independent Disease-Free Prognostic Indicator for Seminoma by Bioinformatic Analysis

A risk prediction model Construction as an Independent Disease-Free Prognostic Indicator for Seminoma by Bioinformatic Analysis

Comprehensive Analysis of the E2F Transcription Factor Family in Human Lung Adenocarcinoma

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

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