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ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types
Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) dataset...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459715/ https://www.ncbi.nlm.nih.gov/pubmed/34568067 http://dx.doi.org/10.3389/fonc.2021.731547 |
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author | Zhang, Wencheng Gao, Zhouyong Guan, Mingxiu Liu, Ning Meng, Fanjie Wang, Guangshun |
author_facet | Zhang, Wencheng Gao, Zhouyong Guan, Mingxiu Liu, Ning Meng, Fanjie Wang, Guangshun |
author_sort | Zhang, Wencheng |
collection | PubMed |
description | Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) datasets revealed the overexpression of ASF1B in all analyzed cancer types other than LAML. Genetic, epigenetic, microsatellite instability (MSI), and tumor mutational burden (TMB) analysis showed that ASF1B was regulated by single or multiple factors. Kaplan-Meier survival curves suggested that elevated ASF1B expression was associated with better or worse survival in a cancer type-dependent manner. The CIBERSORT algorithm was used to evaluate immune microenvironment composition, and distinct correlations between ASF1B expression and immune cell infiltration were evident when comparing tumor and normal tissue samples. Gene set enrichment analysis (GSEA) indicated that ASF1B was associated with proliferation- and immunity-related pathways. Knocking down ASF1B impaired the proliferation, affected cell cycle distribution, and induced cell apoptosis in LUAD cell lines. In contrast, ASF1B overexpression had no impact on the malignant characteristics of LUAD cells. At the mechanistic level, ASF1B served as an indirect regulator of DNA Polymerase Epsilon 3, Accessory Subunit (POLE3), CDC28 protein kinase regulatory subunit 1(CKS1B), Dihydrofolate reductase (DHFR), as established through proteomic profiling and Immunoprecipitation-Mass Spectrometry (IP-MS) analyses. Overall, these data suggested that ASF1B serves as a tumor promoter and potential target for cancer therapy and provided us with clues to better understand the importance of ASF1B in many types of cancer. |
format | Online Article Text |
id | pubmed-8459715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84597152021-09-24 ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types Zhang, Wencheng Gao, Zhouyong Guan, Mingxiu Liu, Ning Meng, Fanjie Wang, Guangshun Front Oncol Oncology Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) datasets revealed the overexpression of ASF1B in all analyzed cancer types other than LAML. Genetic, epigenetic, microsatellite instability (MSI), and tumor mutational burden (TMB) analysis showed that ASF1B was regulated by single or multiple factors. Kaplan-Meier survival curves suggested that elevated ASF1B expression was associated with better or worse survival in a cancer type-dependent manner. The CIBERSORT algorithm was used to evaluate immune microenvironment composition, and distinct correlations between ASF1B expression and immune cell infiltration were evident when comparing tumor and normal tissue samples. Gene set enrichment analysis (GSEA) indicated that ASF1B was associated with proliferation- and immunity-related pathways. Knocking down ASF1B impaired the proliferation, affected cell cycle distribution, and induced cell apoptosis in LUAD cell lines. In contrast, ASF1B overexpression had no impact on the malignant characteristics of LUAD cells. At the mechanistic level, ASF1B served as an indirect regulator of DNA Polymerase Epsilon 3, Accessory Subunit (POLE3), CDC28 protein kinase regulatory subunit 1(CKS1B), Dihydrofolate reductase (DHFR), as established through proteomic profiling and Immunoprecipitation-Mass Spectrometry (IP-MS) analyses. Overall, these data suggested that ASF1B serves as a tumor promoter and potential target for cancer therapy and provided us with clues to better understand the importance of ASF1B in many types of cancer. Frontiers Media S.A. 2021-09-09 /pmc/articles/PMC8459715/ /pubmed/34568067 http://dx.doi.org/10.3389/fonc.2021.731547 Text en Copyright © 2021 Zhang, Gao, Guan, Liu, Meng and Wang https://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 | Oncology Zhang, Wencheng Gao, Zhouyong Guan, Mingxiu Liu, Ning Meng, Fanjie Wang, Guangshun ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title | ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title_full | ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title_fullStr | ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title_full_unstemmed | ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title_short | ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types |
title_sort | asf1b promotes oncogenesis in lung adenocarcinoma and other cancer types |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459715/ https://www.ncbi.nlm.nih.gov/pubmed/34568067 http://dx.doi.org/10.3389/fonc.2021.731547 |
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