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METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer
Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3/LINC00662/miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 19...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537189/ https://www.ncbi.nlm.nih.gov/pubmed/36202872 http://dx.doi.org/10.1038/s41598-022-20477-0 |
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author | Jing, Lei Lan, Liu Mingxin, Zhang Zhaofeng, Zhang |
author_facet | Jing, Lei Lan, Liu Mingxin, Zhang Zhaofeng, Zhang |
author_sort | Jing, Lei |
collection | PubMed |
description | Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3/LINC00662/miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 193 pathologically diagnosed TNBC patients from 2016 to 2017 in our hospital. Quantitative real-time PCR was used to evaluate the expression of LINC00662 and miR-186-5p both in vivo and in vitro. CCK8 tests were used to assess cell viability. ELISA was used for protein expression evaluation. Dual luciferase reporter gene assay and RNA pull-down were used to evaluate the interaction between LINC00662 and miR-186-5p. m6A levels were enhanced in breast cancer tissues and cells. LINC00662, miR-186-5p and METTL3 were differentially expressed in vivo, and METTL3 expression was associated with LINC00662 and miR-186-5p expression. LINC00662 and miR-186-5p were differentially expressed in vitro; LINC00662 promoted cell viability and decreased the apoptosis rate, whereas miR-186-5p inhibited cell viability and increased the apoptosis rate. Furthermore, we found that METTL3 regulated m6A levels in docetaxel-resistant breast cancer cells by regulating the expression of LINC00662. Moreover, LINC00662 and miR-186-5p regulated the cell viability rate of docetaxel-resistant breast cancer cells. Further experiments showed that LINC00662 directly interacted with miR-186-5p to exert biological functions; besides miR-186-5p could regulate the expression of METTL3. METTL3 promotes m6A levels and docetaxel resistance in breast cancer by regulating the expression of LINC00662 and miR-186-5p; more experiments are needed to clarify the role of m6A regulation in drug resistance. |
format | Online Article Text |
id | pubmed-9537189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95371892022-10-08 METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer Jing, Lei Lan, Liu Mingxin, Zhang Zhaofeng, Zhang Sci Rep Article Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3/LINC00662/miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 193 pathologically diagnosed TNBC patients from 2016 to 2017 in our hospital. Quantitative real-time PCR was used to evaluate the expression of LINC00662 and miR-186-5p both in vivo and in vitro. CCK8 tests were used to assess cell viability. ELISA was used for protein expression evaluation. Dual luciferase reporter gene assay and RNA pull-down were used to evaluate the interaction between LINC00662 and miR-186-5p. m6A levels were enhanced in breast cancer tissues and cells. LINC00662, miR-186-5p and METTL3 were differentially expressed in vivo, and METTL3 expression was associated with LINC00662 and miR-186-5p expression. LINC00662 and miR-186-5p were differentially expressed in vitro; LINC00662 promoted cell viability and decreased the apoptosis rate, whereas miR-186-5p inhibited cell viability and increased the apoptosis rate. Furthermore, we found that METTL3 regulated m6A levels in docetaxel-resistant breast cancer cells by regulating the expression of LINC00662. Moreover, LINC00662 and miR-186-5p regulated the cell viability rate of docetaxel-resistant breast cancer cells. Further experiments showed that LINC00662 directly interacted with miR-186-5p to exert biological functions; besides miR-186-5p could regulate the expression of METTL3. METTL3 promotes m6A levels and docetaxel resistance in breast cancer by regulating the expression of LINC00662 and miR-186-5p; more experiments are needed to clarify the role of m6A regulation in drug resistance. Nature Publishing Group UK 2022-10-06 /pmc/articles/PMC9537189/ /pubmed/36202872 http://dx.doi.org/10.1038/s41598-022-20477-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Jing, Lei Lan, Liu Mingxin, Zhang Zhaofeng, Zhang METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title | METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title_full | METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title_fullStr | METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title_full_unstemmed | METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title_short | METTL3/LINC00662/miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
title_sort | mettl3/linc00662/mir-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537189/ https://www.ncbi.nlm.nih.gov/pubmed/36202872 http://dx.doi.org/10.1038/s41598-022-20477-0 |
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