Author
Listed:
- Cong Lv
(College of Biological Sciences, China Agricultural University)
- Fengyin Li
(College of Biological Sciences, China Agricultural University)
- Xiang Li
(College of Biological Sciences, China Agricultural University)
- Yuhua Tian
(College of Biological Sciences, China Agricultural University)
- Yue Zhang
(Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine)
- Xiaole Sheng
(College of Biological Sciences, China Agricultural University)
- Yongli Song
(College of Biological Sciences, China Agricultural University)
- Qingyong Meng
(College of Biological Sciences, China Agricultural University)
- Shukai Yuan
(Basic Medical College, Tianjin Medical University)
- Liming Luan
(Vanderbilt University Medical Center)
- Thomas Andl
(Vanderbilt University Medical Center)
- Xu Feng
(State Key Laboratory of Genetic Resources and Evolution of Kunming Institute of Zoology, Chinese Academy of Sciences)
- Baowei Jiao
(State Key Laboratory of Genetic Resources and Evolution of Kunming Institute of Zoology, Chinese Academy of Sciences)
- Mingang Xu
(Perelman School of Medicine, University of Pennsylvania)
- Maksim V. Plikus
(Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine)
- Xing Dai
(School of Medicine, University of California)
- Christopher Lengner
(School of Veterinary Medicine, University of Pennsylvania
Institute for Regenerative Medicine, University of Pennsylvania
Perelman School of Medicine, University of Pennsylvania)
- Wei Cui
(College of Biological Sciences, China Agricultural University
Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London)
- Fazheng Ren
(College of Biological Sciences, China Agricultural University)
- Jianwei Shuai
(Innovation Center for Cell Signaling Network, Xiamen University)
- Sarah E. Millar
(Perelman School of Medicine, University of Pennsylvania
Perelman School of Medicine, University of Pennsylvania)
- Zhengquan Yu
(College of Biological Sciences, China Agricultural University)
Abstract
MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-κB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFβ and Wnt/β-catenin. Particularly, it activates Wnt/β-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.
Suggested Citation
Cong Lv & Fengyin Li & Xiang Li & Yuhua Tian & Yue Zhang & Xiaole Sheng & Yongli Song & Qingyong Meng & Shukai Yuan & Liming Luan & Thomas Andl & Xu Feng & Baowei Jiao & Mingang Xu & Maksim V. Plikus , 2017.
"MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists,"
Nature Communications, Nature, vol. 8(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01059-5
DOI: 10.1038/s41467-017-01059-5
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