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

8 Scopus citations

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
Publication statusPublished - Jan 1 2017

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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