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The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability
Multiple studies have indicated that circular RNAs (circRNAs) play a regulatory role in different stages of tumors by interacting with various molecules. With continuous in-depth research on the biological functions of circRNAs, increasing evidence has shown that circRNAs play important roles in car...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463561/ https://www.ncbi.nlm.nih.gov/pubmed/36159776 http://dx.doi.org/10.1016/j.omto.2022.08.006 |
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author | Li, Xiaofei Chen, Sixian Wang, Xin Zhang, Ruirui Yang, Jialei Xu, Haotian He, Wanting Lai, Mingshuang Wu, Shuilian Nan, Aruo |
author_facet | Li, Xiaofei Chen, Sixian Wang, Xin Zhang, Ruirui Yang, Jialei Xu, Haotian He, Wanting Lai, Mingshuang Wu, Shuilian Nan, Aruo |
author_sort | Li, Xiaofei |
collection | PubMed |
description | Multiple studies have indicated that circular RNAs (circRNAs) play a regulatory role in different stages of tumors by interacting with various molecules. With continuous in-depth research on the biological functions of circRNAs, increasing evidence has shown that circRNAs play important roles in carcinogenesis caused by environmental pollutants. However, the function and mechanism of circRNAs in arsenic exposure-induced lung cancer occurrence have not been reported. In this study, RNA sequencing and qPCR assays revealed that the expression of circBRWD1 was decreased in BEAS-2B-As cells and multiple lung cancer cell lines. Silencing circBRWD1 promoted cell viability and proliferation, inhibited cell apoptosis, and accelerated the G0/G1 phase transition in BEAS-2B-As cells; however, these functions were abrogated by circBRWD1 overexpression. Mechanistically, under arsenic exposure, expression of decreased circBRWD1 led to enhanced stability of the mRNA to which it directly binds (c-JUN, c-MYC, and CDK6 mRNA), increasing its expression. This mechanism promotes the malignant transformation of lung cells and ultimately leads to lung cancer. Our findings thus reveal the molecular mechanism of arsenic carcinogenesis. |
format | Online Article Text |
id | pubmed-9463561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-94635612022-09-22 The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability Li, Xiaofei Chen, Sixian Wang, Xin Zhang, Ruirui Yang, Jialei Xu, Haotian He, Wanting Lai, Mingshuang Wu, Shuilian Nan, Aruo Mol Ther Oncolytics Original Article Multiple studies have indicated that circular RNAs (circRNAs) play a regulatory role in different stages of tumors by interacting with various molecules. With continuous in-depth research on the biological functions of circRNAs, increasing evidence has shown that circRNAs play important roles in carcinogenesis caused by environmental pollutants. However, the function and mechanism of circRNAs in arsenic exposure-induced lung cancer occurrence have not been reported. In this study, RNA sequencing and qPCR assays revealed that the expression of circBRWD1 was decreased in BEAS-2B-As cells and multiple lung cancer cell lines. Silencing circBRWD1 promoted cell viability and proliferation, inhibited cell apoptosis, and accelerated the G0/G1 phase transition in BEAS-2B-As cells; however, these functions were abrogated by circBRWD1 overexpression. Mechanistically, under arsenic exposure, expression of decreased circBRWD1 led to enhanced stability of the mRNA to which it directly binds (c-JUN, c-MYC, and CDK6 mRNA), increasing its expression. This mechanism promotes the malignant transformation of lung cells and ultimately leads to lung cancer. Our findings thus reveal the molecular mechanism of arsenic carcinogenesis. American Society of Gene & Cell Therapy 2022-08-23 /pmc/articles/PMC9463561/ /pubmed/36159776 http://dx.doi.org/10.1016/j.omto.2022.08.006 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Li, Xiaofei Chen, Sixian Wang, Xin Zhang, Ruirui Yang, Jialei Xu, Haotian He, Wanting Lai, Mingshuang Wu, Shuilian Nan, Aruo The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title | The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title_full | The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title_fullStr | The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title_full_unstemmed | The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title_short | The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability |
title_sort | pivotal regulatory factor circbrwd1 inhibits arsenic exposure-induced lung cancer occurrence by binding mrna and regulating its stability |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463561/ https://www.ncbi.nlm.nih.gov/pubmed/36159776 http://dx.doi.org/10.1016/j.omto.2022.08.006 |
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