MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells
Stem-like cells in tumor group featured the major role in the chemotherapy resistance of breast cancer, and the reduction of stem-like cells helped to perish the tumor when receiving chemotherapy. Smaller stem cells number indicated better therapeutic effect in vitro and in clinics, but how did miR-...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732725/ https://www.ncbi.nlm.nih.gov/pubmed/29262559 http://dx.doi.org/10.18632/oncotarget.21143 |
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author | Xiao, Guodong Li, Xiang Li, Gang Zhang, Boxiang Xu, Chongwen Qin, Sida Du, Ning Wang, Jichang Tang, Shou-Ching Zhang, Jing Ren, Hong Chen, Ke Sun, Xin |
author_facet | Xiao, Guodong Li, Xiang Li, Gang Zhang, Boxiang Xu, Chongwen Qin, Sida Du, Ning Wang, Jichang Tang, Shou-Ching Zhang, Jing Ren, Hong Chen, Ke Sun, Xin |
author_sort | Xiao, Guodong |
collection | PubMed |
description | Stem-like cells in tumor group featured the major role in the chemotherapy resistance of breast cancer, and the reduction of stem-like cells helped to perish the tumor when receiving chemotherapy. Smaller stem cells number indicated better therapeutic effect in vitro and in clinics, but how did miR-129 and Notch signaling function in breast cancer stem-like cells (BrCSCs) were unclear yet. Through using sphere forming assay and FACS sorting, we found that miR-129 decreased the proportion of stem-like cells in breast cancer cells. Results further indicated that miR-129 degraded the Estrogen Receptor 1 (ESR1) mRNA through a post-translational manner and contributed to the decline of stem-like cells number, preventing tumor regeneration. Cyclin d1 and DICER 1 were proved to promote Let-7 maturation, and in present study, we proved that miR-129 exhibited inhibition on ESR1 and halted the cyclin d1/DICER 1 sustaining of Let-7, which consequently released the Let-7 degradation of NUMB. The restoration of suppressive NUMB by upregulating miR-129 resulted in NOTCH signaling inhibition. In conclusion, we demonstrated the negative regulation of miR-129 on NOTCH signaling activation in BrCSCs’ renewal, which was achieved via continuous suppression on cyclin d1/DICER1 sustaining of Let-7 level, and eventually rescued the targeted inhibition of NUMB. The miR-129/ESR1 signaling played pivotal role in controlling DICER1/Let-7/NOTCH cascade via cyclin d1, revealing the novel mechanism of dual Let-7 in non-coding genes network. |
format | Online Article Text |
id | pubmed-5732725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57327252017-12-19 MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells Xiao, Guodong Li, Xiang Li, Gang Zhang, Boxiang Xu, Chongwen Qin, Sida Du, Ning Wang, Jichang Tang, Shou-Ching Zhang, Jing Ren, Hong Chen, Ke Sun, Xin Oncotarget Research Paper Stem-like cells in tumor group featured the major role in the chemotherapy resistance of breast cancer, and the reduction of stem-like cells helped to perish the tumor when receiving chemotherapy. Smaller stem cells number indicated better therapeutic effect in vitro and in clinics, but how did miR-129 and Notch signaling function in breast cancer stem-like cells (BrCSCs) were unclear yet. Through using sphere forming assay and FACS sorting, we found that miR-129 decreased the proportion of stem-like cells in breast cancer cells. Results further indicated that miR-129 degraded the Estrogen Receptor 1 (ESR1) mRNA through a post-translational manner and contributed to the decline of stem-like cells number, preventing tumor regeneration. Cyclin d1 and DICER 1 were proved to promote Let-7 maturation, and in present study, we proved that miR-129 exhibited inhibition on ESR1 and halted the cyclin d1/DICER 1 sustaining of Let-7, which consequently released the Let-7 degradation of NUMB. The restoration of suppressive NUMB by upregulating miR-129 resulted in NOTCH signaling inhibition. In conclusion, we demonstrated the negative regulation of miR-129 on NOTCH signaling activation in BrCSCs’ renewal, which was achieved via continuous suppression on cyclin d1/DICER1 sustaining of Let-7 level, and eventually rescued the targeted inhibition of NUMB. The miR-129/ESR1 signaling played pivotal role in controlling DICER1/Let-7/NOTCH cascade via cyclin d1, revealing the novel mechanism of dual Let-7 in non-coding genes network. Impact Journals LLC 2017-09-21 /pmc/articles/PMC5732725/ /pubmed/29262559 http://dx.doi.org/10.18632/oncotarget.21143 Text en Copyright: © 2017 Xiao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xiao, Guodong Li, Xiang Li, Gang Zhang, Boxiang Xu, Chongwen Qin, Sida Du, Ning Wang, Jichang Tang, Shou-Ching Zhang, Jing Ren, Hong Chen, Ke Sun, Xin MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title | MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title_full | MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title_fullStr | MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title_full_unstemmed | MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title_short | MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells |
title_sort | mir-129 blocks estrogen induction of notch signaling activity in breast cancer stem-like cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732725/ https://www.ncbi.nlm.nih.gov/pubmed/29262559 http://dx.doi.org/10.18632/oncotarget.21143 |
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