MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells

Guodong Xiao, Xiang Li, Gang Li, Boxiang Zhang, Chongwen Xu, Sida Qin, Ning Du, Jichang Wang, Shou-Ching Tang, Jing Zhang, Hong Ren, Ke Chen, Xin Sun

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)103261-103273
Number of pages13
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - Jan 1 2017

Fingerprint

Neoplastic Stem Cells
Cyclin D1
Estrogens
Stem Cells
Estrogen Receptor alpha
Breast Neoplasms
Cell Count
Drug Therapy
Neoplasms
Gene Regulatory Networks
Therapeutic Uses
Regeneration
Messenger RNA

Keywords

  • DICER1
  • ESR1
  • Let-7
  • MiR-129
  • NOTCH signaling

ASJC Scopus subject areas

  • Oncology

Cite this

Xiao, G., Li, X., Li, G., Zhang, B., Xu, C., Qin, S., ... Sun, X. (2017). MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells. Oncotarget, 8(61), 103261-103273. https://doi.org/10.18632/oncotarget.21143

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.

In: Oncotarget, Vol. 8, No. 61, 01.01.2017, p. 103261-103273.

Research output: Contribution to journalArticle

Xiao, G, Li, X, Li, G, Zhang, B, Xu, C, Qin, S, Du, N, Wang, J, Tang, S-C, Zhang, J, Ren, H, Chen, K & Sun, X 2017, 'MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells', Oncotarget, vol. 8, no. 61, pp. 103261-103273. https://doi.org/10.18632/oncotarget.21143
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. In: Oncotarget. 2017 ; Vol. 8, No. 61. pp. 103261-103273.
@article{db95dc20162f4045868c9c3b013cd00e,
title = "MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells",
abstract = "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.",
keywords = "DICER1, ESR1, Let-7, MiR-129, NOTCH signaling",
author = "Guodong Xiao and Xiang Li and Gang Li and Boxiang Zhang and Chongwen Xu and Sida Qin and Ning Du and Jichang Wang and Shou-Ching Tang and Jing Zhang and Hong Ren and Ke Chen and Xin Sun",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.21143",
language = "English (US)",
volume = "8",
pages = "103261--103273",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "61",

}

TY - JOUR

T1 - MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells

AU - Xiao, Guodong

AU - Li, Xiang

AU - Li, Gang

AU - Zhang, Boxiang

AU - Xu, Chongwen

AU - Qin, Sida

AU - Du, Ning

AU - Wang, Jichang

AU - Tang, Shou-Ching

AU - Zhang, Jing

AU - Ren, Hong

AU - Chen, Ke

AU - Sun, Xin

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - DICER1

KW - ESR1

KW - Let-7

KW - MiR-129

KW - NOTCH signaling

UR - http://www.scopus.com/inward/record.url?scp=85035319626&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035319626&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.21143

DO - 10.18632/oncotarget.21143

M3 - Article

VL - 8

SP - 103261

EP - 103273

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 61

ER -