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Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma

BACKGROUND: YTH domain family (YTHDF) 2 acts as a “reader” protein for RNA methylation, which is important in tumor regulation. However, the effect of YTHDF2 in liver hepatocellular carcinoma (LIHC) has yet to be elucidated. METHODS: We explored the role of YTHDF2 in LIHC based on publicly available...

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Autores principales: Shao, Xiang-yang, Dong, Jin, Zhang, Han, Wu, Ying-song, Zheng, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738478/
https://www.ncbi.nlm.nih.gov/pubmed/33344502
http://dx.doi.org/10.3389/fmolb.2020.577460
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author Shao, Xiang-yang
Dong, Jin
Zhang, Han
Wu, Ying-song
Zheng, Lei
author_facet Shao, Xiang-yang
Dong, Jin
Zhang, Han
Wu, Ying-song
Zheng, Lei
author_sort Shao, Xiang-yang
collection PubMed
description BACKGROUND: YTH domain family (YTHDF) 2 acts as a “reader” protein for RNA methylation, which is important in tumor regulation. However, the effect of YTHDF2 in liver hepatocellular carcinoma (LIHC) has yet to be elucidated. METHODS: We explored the role of YTHDF2 in LIHC based on publicly available datasets [The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO)]. A bioinformatics approach was employed to analyze YTHDF2. Logistic regression analyses were applied to analyze the correlation between YTHDF2 expression and clinical characteristics. To evaluate the effect of YTHDF2 on the prognosis of LIHC patients, we used Kaplan–Meier (K–M) curves. Gene set enrichment analysis (GSEA) was undertaken using TCGA dataset. Univariate and multivariate Cox analyses were used to ascertain the correlations between YTHDF2 expression and clinicopathologic characteristics with survival. Genes co-expressed with YTHDF2 were identified and detected using publicly available datasets [LinkedOmics, University of California, Santa Cruz (UCSC), Gene Expression Profiling Interactive Analysis (GEPIA), and GEO]. Correlations between YTHDF2 and infiltration of immune cells were investigated by Tumor Immune Estimation Resource (TIMER) and GEPIA. RESULTS: mRNA and protein expression of YTHDF2 was significantly higher in LIHC tissues than in non-cancerous tissues. High YTHDF2 expression in LIHC was associated with poor prognostic clinical factors (high stage, grade, and T classification). K–M analyses indicated that high YTHDF2 expression was correlated with an unfavorable prognosis. Univariate and multivariate Cox analyses revealed that YTHDF2 was an independent factor for a poor prognosis in LIHC patients. GSEA revealed that the high-expression phenotype of YTHDF2 was consistent with the molecular pathways implicated in LIHC carcinogenesis. Analyses of receiver operating characteristic curves showed that YTHDF2 might have a diagnostic value in LIHC patients. YTHDF2 expression was associated positively with SF3A3 expression, which implied that they may cooperate in LIHC progression. YTHDF2 expression was associated with infiltration of immune cells and their marker genes. YTHDF2 had the potential to regulate polarization of tumor-associated macrophages, induce T-cell exhaustion, and activate T-regulatory cells. CONCLUSION: YTHDF2 may be a promising biomarker for the diagnosis and prognosis of LIHC and may provide new directions and strategies for LIHC treatment.
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spelling pubmed-77384782020-12-17 Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma Shao, Xiang-yang Dong, Jin Zhang, Han Wu, Ying-song Zheng, Lei Front Mol Biosci Molecular Biosciences BACKGROUND: YTH domain family (YTHDF) 2 acts as a “reader” protein for RNA methylation, which is important in tumor regulation. However, the effect of YTHDF2 in liver hepatocellular carcinoma (LIHC) has yet to be elucidated. METHODS: We explored the role of YTHDF2 in LIHC based on publicly available datasets [The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO)]. A bioinformatics approach was employed to analyze YTHDF2. Logistic regression analyses were applied to analyze the correlation between YTHDF2 expression and clinical characteristics. To evaluate the effect of YTHDF2 on the prognosis of LIHC patients, we used Kaplan–Meier (K–M) curves. Gene set enrichment analysis (GSEA) was undertaken using TCGA dataset. Univariate and multivariate Cox analyses were used to ascertain the correlations between YTHDF2 expression and clinicopathologic characteristics with survival. Genes co-expressed with YTHDF2 were identified and detected using publicly available datasets [LinkedOmics, University of California, Santa Cruz (UCSC), Gene Expression Profiling Interactive Analysis (GEPIA), and GEO]. Correlations between YTHDF2 and infiltration of immune cells were investigated by Tumor Immune Estimation Resource (TIMER) and GEPIA. RESULTS: mRNA and protein expression of YTHDF2 was significantly higher in LIHC tissues than in non-cancerous tissues. High YTHDF2 expression in LIHC was associated with poor prognostic clinical factors (high stage, grade, and T classification). K–M analyses indicated that high YTHDF2 expression was correlated with an unfavorable prognosis. Univariate and multivariate Cox analyses revealed that YTHDF2 was an independent factor for a poor prognosis in LIHC patients. GSEA revealed that the high-expression phenotype of YTHDF2 was consistent with the molecular pathways implicated in LIHC carcinogenesis. Analyses of receiver operating characteristic curves showed that YTHDF2 might have a diagnostic value in LIHC patients. YTHDF2 expression was associated positively with SF3A3 expression, which implied that they may cooperate in LIHC progression. YTHDF2 expression was associated with infiltration of immune cells and their marker genes. YTHDF2 had the potential to regulate polarization of tumor-associated macrophages, induce T-cell exhaustion, and activate T-regulatory cells. CONCLUSION: YTHDF2 may be a promising biomarker for the diagnosis and prognosis of LIHC and may provide new directions and strategies for LIHC treatment. Frontiers Media S.A. 2020-12-02 /pmc/articles/PMC7738478/ /pubmed/33344502 http://dx.doi.org/10.3389/fmolb.2020.577460 Text en Copyright © 2020 Shao, Dong, Zhang, Wu and Zheng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Shao, Xiang-yang
Dong, Jin
Zhang, Han
Wu, Ying-song
Zheng, Lei
Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title_full Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title_fullStr Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title_full_unstemmed Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title_short Systematic Analyses of the Role of the Reader Protein of N(6)-Methyladenosine RNA Methylation, YTH Domain Family 2, in Liver Hepatocellular Carcinoma
title_sort systematic analyses of the role of the reader protein of n(6)-methyladenosine rna methylation, yth domain family 2, in liver hepatocellular carcinoma
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738478/
https://www.ncbi.nlm.nih.gov/pubmed/33344502
http://dx.doi.org/10.3389/fmolb.2020.577460
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