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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.616098/full |
| _version_ | 1818573168930979840 |
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| author | Xianneng Sheng Jinqiu Wang Yu Guo Jiabo Zhang Jin Luo |
| author_facet | Xianneng Sheng Jinqiu Wang Yu Guo Jiabo Zhang Jin Luo |
| author_sort | Xianneng Sheng |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-15T00:07:28Z |
| format | Article |
| id | doaj.art-765197f1847242a59d77809f5377329f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-15T00:07:28Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-765197f1847242a59d77809f5377329f2022-12-21T22:42:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011010.3389/fonc.2020.616098616098DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast CancerXianneng ShengJinqiu WangYu GuoJiabo ZhangJin LuoTriple 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.https://www.frontiersin.org/articles/10.3389/fonc.2020.616098/fulltriple negative breast cancer (TNBC)6mAMDA-MB-231Olaparib resistanceLINP1 |
| spellingShingle | Xianneng Sheng Jinqiu Wang Yu Guo Jiabo Zhang Jin Luo DNA N6-Methyladenine (6mA) Modification Regulates Drug Resistance in Triple Negative Breast Cancer Frontiers in Oncology triple negative breast cancer (TNBC) 6mA MDA-MB-231 Olaparib resistance LINP1 |
| 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 | triple negative breast cancer (TNBC) 6mA MDA-MB-231 Olaparib resistance LINP1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.616098/full |
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