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-...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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