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...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.731547/full |
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| author | Wencheng Zhang Zhouyong Gao Mingxiu Guan Ning Liu Fanjie Meng Guangshun Wang |
| author_facet | Wencheng Zhang Zhouyong Gao Mingxiu Guan Ning Liu Fanjie Meng Guangshun Wang |
| author_sort | Wencheng Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T04:49:58Z |
| format | Article |
| id | doaj.art-17b1ceaa1ff34b51a8fd0136a7bb3863 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T04:49:58Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-17b1ceaa1ff34b51a8fd0136a7bb38632022-12-21T18:38:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.731547731547ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer TypesWencheng Zhang0Zhouyong Gao1Mingxiu Guan2Ning Liu3Fanjie Meng4Guangshun Wang5Department of Oncology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, ChinaDepartment of Thoracic Surgery, Baodi Clinical College of Tianjin Medical University, Tianjin, ChinaDepartment of Laboratory, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, ChinaDepartment of Pathology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, ChinaDepartment of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Oncology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, ChinaAnti-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.https://www.frontiersin.org/articles/10.3389/fonc.2021.731547/fulllung adenocarcinomaimmune infiltration cellsprognosisASF1Bprofiling |
| spellingShingle | Wencheng Zhang Zhouyong Gao Mingxiu Guan Ning Liu Fanjie Meng Guangshun Wang ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types Frontiers in Oncology lung adenocarcinoma immune infiltration cells prognosis ASF1B profiling |
| 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 | lung adenocarcinoma immune infiltration cells prognosis ASF1B profiling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.731547/full |
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