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DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer
Triple negative breast cancer (TNBC) is a subtype of breast cancer with strong aggressiveness and poor clinical treatment effect, accounting for about 10–20% of breast cancer cases. N(6)-methyldeoxyadenosine (6mA) is the most conservative DNA modification in prokaryotes and eukaryotes. It is widely...
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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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887291/ https://www.ncbi.nlm.nih.gov/pubmed/33614498 http://dx.doi.org/10.3389/fonc.2020.616098 |
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author | Sheng, Xianneng Wang, Jinqiu Guo, Yu Zhang, Jiabo Luo, Jin |
author_facet | Sheng, Xianneng Wang, Jinqiu Guo, Yu Zhang, Jiabo Luo, Jin |
author_sort | Sheng, Xianneng |
collection | PubMed |
description | Triple negative breast cancer (TNBC) is a subtype of breast cancer with strong aggressiveness and poor clinical treatment effect, accounting for about 10–20% of breast cancer cases. N(6)-methyldeoxyadenosine (6mA) is the most conservative DNA modification in prokaryotes and eukaryotes. It is widely found in bacteria and has such functions as DNA mismatch repair, chromosome separation and virulence regulation. We determined that 6mA was modified in TNBC cell line MDA-MB-231 and the TNBC tissue. Meanwhile, compared with normal tissues, the expression level of 6mA and its methylase N6AMT1 was significantly decreased in TNBC tissue. MDA-MB-231cells were cultured with 8μM Olaparib for 2 months to construct drug-resistant cell line 231-RO. It was found that the level of 6mA also increased significantly, and the expression of N6AMT1 or ALKBH1 could effectively influence the drug resistance. Subsequently, we found that LINP1 was highly expressed in 231-RO, which was involved in DNA repair, and the expression of LINP1 could be positively regulated by 6mA modification. LINP1 expression level is directly related to TNBC drug resistance. The above results indicate that 6mA may be a new biological marker of TNBC. Meanwhile, 6mA modification may be involved in the regulation of Olaparib resistance. |
format | Online Article Text |
id | pubmed-7887291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78872912021-02-18 DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer Sheng, Xianneng Wang, Jinqiu Guo, Yu Zhang, Jiabo Luo, Jin Front Oncol Oncology Triple negative breast cancer (TNBC) is a subtype of breast cancer with strong aggressiveness and poor clinical treatment effect, accounting for about 10–20% of breast cancer cases. N(6)-methyldeoxyadenosine (6mA) is the most conservative DNA modification in prokaryotes and eukaryotes. It is widely found in bacteria and has such functions as DNA mismatch repair, chromosome separation and virulence regulation. We determined that 6mA was modified in TNBC cell line MDA-MB-231 and the TNBC tissue. Meanwhile, compared with normal tissues, the expression level of 6mA and its methylase N6AMT1 was significantly decreased in TNBC tissue. MDA-MB-231cells were cultured with 8μM Olaparib for 2 months to construct drug-resistant cell line 231-RO. It was found that the level of 6mA also increased significantly, and the expression of N6AMT1 or ALKBH1 could effectively influence the drug resistance. Subsequently, we found that LINP1 was highly expressed in 231-RO, which was involved in DNA repair, and the expression of LINP1 could be positively regulated by 6mA modification. LINP1 expression level is directly related to TNBC drug resistance. The above results indicate that 6mA may be a new biological marker of TNBC. Meanwhile, 6mA modification may be involved in the regulation of Olaparib resistance. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7887291/ /pubmed/33614498 http://dx.doi.org/10.3389/fonc.2020.616098 Text en Copyright © 2021 Sheng, Wang, Guo, Zhang and Luo http://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 Sheng, Xianneng Wang, Jinqiu Guo, Yu Zhang, Jiabo Luo, Jin DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title | DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title_full | DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title_fullStr | DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title_full_unstemmed | DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title_short | DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer |
title_sort | dna n6-methyladenine (6ma) modification regulates drug resistance in triple negative breast cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887291/ https://www.ncbi.nlm.nih.gov/pubmed/33614498 http://dx.doi.org/10.3389/fonc.2020.616098 |
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