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Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells

Cancer Gene Therapy volume 23, pages 83–89 (2016)Cite this article

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Abstract

Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family members in clinical tissues, we found that higher expression levels of let-7b and let-7c were correlated with better clinical prognosis of patients with estrogen receptor (ER)α-positive breast tumor. Further, we found that only let-7c was inversely correlated with ERα expression, and there is corelationship between let-7c and Wnt signaling in clinical tissues. Aldehyde dehydrogenase (ALDH)1 sorting and mammosphere formation assays showed that let-7c inhibited the self-renewal of stem cells in ERα-positive breast cancer. Let-7c decreased ERα expression through directly binding to the 3’UTR (untranslated region), and let-7c inhibited the estrogen-induced activation of Wnt signaling. Depletion of ERα abolished let-7c functions in stem cell signatures, which further confirmed that let-7c inhibited estrogen-induced Wnt activity through decreasing ERα expression. Taken together, our findings identified a biochemical and functional link between let-7c with ERα/Wnt signaling in breast cancer stem cells.

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Acknowledgements

The authors acknowledge assistants in the Key Laboratory (Ministry of Education) of Environment and Genes Related to Disease, and the Center for Translational Medicine of The First Affiliated Hospital of Xi’an Jiaotong University, for their technical assistance. This experiment was mainly supported by National Natural Science Foundation of China, grant no. 81272418 (HR). This work was also supported in part by National Science Foundation for Young Scientists of China, grant no. 81502227 (SHX) and 81402506 (SDQ). All co-authors implicated in this research approved this article to be published.

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Author notes

  1. X Sun and C Xu: Equal contribution as co-first authors.

Authors and Affiliations

  1. Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China

    X Sun, H Wang, P Wang, N Du, S Qin, G Li, Dapeng Liu & H Ren

  2. Department of Otorhinolaryngology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China

    C Xu

  3. Breast Cancer Program and Interdisciplinary Translational Research Team, Georgia Regents University Cancer Center, Augusta, Georgia, USA

    S-C Tang

  4. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    S-C Tang

  5. Department of Vascular and Endovascular Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China

    J Wang

  6. Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

    S Xu

  7. Department of Radiation Oncology, Tianjin Cancer Institute and Hospital Affiliated to Tianjin Medical University, Tianjin, China

    Z Tao

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Correspondence to H Ren.

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Sun, X., Xu, C., Tang, SC. et al. Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells. Cancer Gene Ther 23, 83–89 (2016). https://doi.org/10.1038/cgt.2016.3

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  • DOI: https://doi.org/10.1038/cgt.2016.3

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