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Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer

BACKGROUND: The histone methyltransferase (HMT) family includes histone lysine methyltransferases (HKMTs) and histone/protein arginine methyltransferases (PRMTs). The role of HMT gene variants in prostate cancer remains unknown. Therefore, this study aimed to evaluate HMT gene variants in the pathog...

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Autores principales: Zhang, Yangjun, Yan, Libin, Yao, Weimin, Chen, Ke, Xu, Hua, Ye, Zhangqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330996/
https://www.ncbi.nlm.nih.gov/pubmed/30616239
http://dx.doi.org/10.12659/MSM.912294
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author Zhang, Yangjun
Yan, Libin
Yao, Weimin
Chen, Ke
Xu, Hua
Ye, Zhangqun
author_facet Zhang, Yangjun
Yan, Libin
Yao, Weimin
Chen, Ke
Xu, Hua
Ye, Zhangqun
author_sort Zhang, Yangjun
collection PubMed
description BACKGROUND: The histone methyltransferase (HMT) family includes histone lysine methyltransferases (HKMTs) and histone/protein arginine methyltransferases (PRMTs). The role of HMT gene variants in prostate cancer remains unknown. Therefore, this study aimed to evaluate HMT gene variants in the pathogenesis and prognosis of human prostate cancer, using in vitro cell studies and bioinformatics analysis. MATERIAL/METHODS: Integrative bioinformatics analysis of the expression of 51 HMT genes in human prostate cancer was based on datasets from the Cancer Genome Atlas (TCGA). Correlation and regression analysis were used to identify critical HMTs in prostate cancer. Kaplan-Meier and the area under the receiver operating characteristics curve (AUROC) were performed to evaluate the function of the HMTs on prognosis. Gene expression and function of 22Rv1 human prostate carcinoma cells were studied. RESULTS: The HMT genes identified to have a role in the pathogenesis of prostate cancer included the EZH2, SETD5, PRDM12, NSD1, SETD6, SMYD1, and the WHSC1L1 gene. The EZH2, SETD5, and SMYD1 genes were selected as a prognostic panel, with the SUV420H2 HMT gene. SETD2, NSD1, and ASH1L were identified as critical genes in the development of castration-resistant prostate cancer (CRPC), similar to mixed-lineage leukemia (MLL) complex family members. Knockdown of the SETD5 gene in 22Rv1 prostate carcinoma cells in vitro inhibited cancer cell growth and migration. CONCLUSIONS: HMT gene variants may have a role in the pathogenesis of prostate cancer. Future studies may determine the role of HMT genes as prognostic biomarkers in patients with prostate cancer.
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spelling pubmed-63309962019-01-29 Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer Zhang, Yangjun Yan, Libin Yao, Weimin Chen, Ke Xu, Hua Ye, Zhangqun Med Sci Monit Lab/In Vitro Research BACKGROUND: The histone methyltransferase (HMT) family includes histone lysine methyltransferases (HKMTs) and histone/protein arginine methyltransferases (PRMTs). The role of HMT gene variants in prostate cancer remains unknown. Therefore, this study aimed to evaluate HMT gene variants in the pathogenesis and prognosis of human prostate cancer, using in vitro cell studies and bioinformatics analysis. MATERIAL/METHODS: Integrative bioinformatics analysis of the expression of 51 HMT genes in human prostate cancer was based on datasets from the Cancer Genome Atlas (TCGA). Correlation and regression analysis were used to identify critical HMTs in prostate cancer. Kaplan-Meier and the area under the receiver operating characteristics curve (AUROC) were performed to evaluate the function of the HMTs on prognosis. Gene expression and function of 22Rv1 human prostate carcinoma cells were studied. RESULTS: The HMT genes identified to have a role in the pathogenesis of prostate cancer included the EZH2, SETD5, PRDM12, NSD1, SETD6, SMYD1, and the WHSC1L1 gene. The EZH2, SETD5, and SMYD1 genes were selected as a prognostic panel, with the SUV420H2 HMT gene. SETD2, NSD1, and ASH1L were identified as critical genes in the development of castration-resistant prostate cancer (CRPC), similar to mixed-lineage leukemia (MLL) complex family members. Knockdown of the SETD5 gene in 22Rv1 prostate carcinoma cells in vitro inhibited cancer cell growth and migration. CONCLUSIONS: HMT gene variants may have a role in the pathogenesis of prostate cancer. Future studies may determine the role of HMT genes as prognostic biomarkers in patients with prostate cancer. International Scientific Literature, Inc. 2019-01-07 /pmc/articles/PMC6330996/ /pubmed/30616239 http://dx.doi.org/10.12659/MSM.912294 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Zhang, Yangjun
Yan, Libin
Yao, Weimin
Chen, Ke
Xu, Hua
Ye, Zhangqun
Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title_full Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title_fullStr Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title_full_unstemmed Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title_short Integrated Analysis of Genetic Abnormalities of the Histone Lysine Methyltransferases in Prostate Cancer
title_sort integrated analysis of genetic abnormalities of the histone lysine methyltransferases in prostate cancer
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330996/
https://www.ncbi.nlm.nih.gov/pubmed/30616239
http://dx.doi.org/10.12659/MSM.912294
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