Research Papers:

This article has been corrected. Correction in: Oncotarget. 2023; 14:809-809.

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 and Xin Sun _

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Oncotarget. 2017; 8:103261-103273. https://doi.org/10.18632/oncotarget.21143

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Guodong Xiao1,*, Xiang Li1,*, Gang Li1,*, Boxiang Zhang1, Chongwen Xu2, Sida Qin1, Ning Du1, Jichang Wang3, Shou-Ching Tang4,5, Jing Zhang1, Hong Ren1, Ke Chen6 and Xin Sun1

1Department of Thoracic Surgery and Oncology, The Second Department of Thoracic Surgery, Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

2Department of Otorhinolaryngology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

3Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an 710061, China

4Breast Cancer Program and Interdisciplinary Translational Research Team, Georgia Regents University Cancer Center, Augusta, Georgia 30912, United States

5Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

6Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

*These authors are considered as co-first authors

Correspondence to:

Xin Sun, email: [email protected]

Ke Chen, email: [email protected]

Keywords: miR-129, ESR1, DICER1, Let-7, NOTCH signaling

Received: March 24, 2017     Accepted: August 08, 2017     Published: September 21, 2017


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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