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Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract

Background and Objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation proces...

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Autores principales: Duan, Shuyin, Yuan, Huijie, Yu, Songcheng, Wei, Xiaoling, Zhou, Xiaoshan, Wang, Wei, Feng, Feifei, Qu, Lingbo, Wu, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823543/
https://www.ncbi.nlm.nih.gov/pubmed/33383878
http://dx.doi.org/10.3390/medicina57010024
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author Duan, Shuyin
Yuan, Huijie
Yu, Songcheng
Wei, Xiaoling
Zhou, Xiaoshan
Wang, Wei
Feng, Feifei
Qu, Lingbo
Wu, Yongjun
author_facet Duan, Shuyin
Yuan, Huijie
Yu, Songcheng
Wei, Xiaoling
Zhou, Xiaoshan
Wang, Wei
Feng, Feifei
Qu, Lingbo
Wu, Yongjun
author_sort Duan, Shuyin
collection PubMed
description Background and Objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Material and Methods: BEAS-2B cells treated with 3.0 μg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.
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spelling pubmed-78235432021-01-24 Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract Duan, Shuyin Yuan, Huijie Yu, Songcheng Wei, Xiaoling Zhou, Xiaoshan Wang, Wei Feng, Feifei Qu, Lingbo Wu, Yongjun Medicina (Kaunas) Article Background and Objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Material and Methods: BEAS-2B cells treated with 3.0 μg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer. MDPI 2020-12-29 /pmc/articles/PMC7823543/ /pubmed/33383878 http://dx.doi.org/10.3390/medicina57010024 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Duan, Shuyin
Yuan, Huijie
Yu, Songcheng
Wei, Xiaoling
Zhou, Xiaoshan
Wang, Wei
Feng, Feifei
Qu, Lingbo
Wu, Yongjun
Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title_full Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title_fullStr Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title_full_unstemmed Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title_short Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract
title_sort epigenetic-based biomarkers in the malignant transformation of beas-2b cells induced by coal tar pitch extract
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823543/
https://www.ncbi.nlm.nih.gov/pubmed/33383878
http://dx.doi.org/10.3390/medicina57010024
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