Breast cancer stem-like cells are sensitized to tamoxifen induction of self-renewal inhibition with enforced Let-7c dependent on Wnt blocking

Xin Sun, Chongwen Xu, Guodong Xiao, Jinying Meng, Jichang Wang, Shou-Ching Tang, Sida Qin, Ning Du, Gang Li, Hong Ren, Dapeng Liu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Let-7 microRNA s have been reported to have tumor suppressive functions; however, the effect of Let-7 when used in combination with chemotherapies is uncertain, but may have potential for use in clinical practice. In this study, we used RT-qPCR , western blot analysis, cell proliferation assay, flow cytometry analysis, immunohistochemistry (IHC) staining, luciferase assays, cell sorting analysis and xenografted tumor model to explore the role of Let-7 in the chemotherapy sensitivity of breast cancer stem cells. The findings of the current study indicated that Let-7 enhances the effects of endocrine therapy potentially by regulating the self-renewal of cancer stem cells. Let-7c increased the anticancer functions of tamoxifen and reduced the ratio of cancer stem-like cells (CSCs), sensitizing cells to therapy-induced repression in an estrogen receptor (ER )-dependent manner. Notably, Let-7 decreased the tumor formation ability of estrogen-Treated breast CSCs in vivo and suppressed Wnt signaling, which further consolidated the previously hypothesis that Let-7 decreases the self-renewal ability, contributing to reduced tumor formation ability of stem cells. The suppressive effects exerted by Let-7 on stem-like cells involved Let-7c/ER /Wnt signaling, and the functions of Let-7c exerted with tamoxifen were dependent on ER. Taken together, the findings identified a biochemical and functional link between Let-7 and endocrine therapy in breast CSCs, which may facilitate clinical treatment in the future using delivery of suppressive Let-7.

Original languageEnglish (US)
Pages (from-to)1967-1975
Number of pages9
JournalInternational journal of molecular medicine
Volume41
Issue number4
DOIs
StatePublished - Apr 2018

Keywords

  • Breast cancer
  • Cancer stem-like cells
  • Endocrine therapy
  • Estrogen receptor
  • Let-7 microRNA s
  • Tamoxifen

ASJC Scopus subject areas

  • Genetics

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