MicroRNA100 Inhibits Self-renewal of Breast Cancer Stem-like Cells and Breast Tumor Development

Overview

Journal Cancer Res

Specialty Oncology

Date 2014 Sep 14

PMID 25217527

Citations 36

Authors

Lu Deng

Li Shang

Shoumin Bai

Ji Chen

Xueyan He

Rachel Martin-Trevino

Shanshan Chen

Xiao-Yan Li

Xiaojie Meng

Bin Yu

Xiaolin Wang

Yajing Liu

Sean P McDermott

Alexa E Ariazi

Christophe Ginestier

Ingrid Ibarra

Jia Ke

Tahra Luther

Shawn G Clouthier

Liang Xu

Ge Shan

Erwei Song

Herui Yao

Gregory J Hannon

Stephen J Weiss

Max S Wicha

Suling Liu

Affiliations

Soon will be listed here.

Abstract

miRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here, we report evidence implicating the miR100 in self-renewal of cancer stem-like cells (CSC). We found that miR100 expression levels relate to the cellular differentiation state, with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR100 in human cells, we found that increasing miR100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1, and BMPR2. Furthermore, miR100 induction in breast CSCs immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR100 expression in breast cancer specimens and patient survival. Our results suggest that miR100 is required to direct CSC self-renewal and differentiation.

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References

Xu L, Huang C, Huang W, Tang W, Rait A, Yin Y . Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Mol Cancer Ther. 2002; 1(5):337-46. View

Yang H, Kong W, He L, Zhao J, ODonnell J, Wang J . MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008; 68(2):425-33. DOI: 10.1158/0008-5472.CAN-07-2488. View

Lu C, Li X, Hu Y, Rowe R, Weiss S . MT1-MMP controls human mesenchymal stem cell trafficking and differentiation. Blood. 2009; 115(2):221-9. PMC: 2808151. DOI: 10.1182/blood-2009-06-228494. View

Hauptschein R, Sloan K, Torella C, Moezzifard R, Giel-Moloney M, Zehetmeier C . Functional proteomic screen identifies a modulating role for CD44 in death receptor-mediated apoptosis. Cancer Res. 2005; 65(5):1887-96. DOI: 10.1158/0008-5472.CAN-04-3571. View

Ginestier C, Hur M, Charafe-Jauffret E, Monville F, Dutcher J, Brown M . ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2008; 1(5):555-67. PMC: 2423808. DOI: 10.1016/j.stem.2007.08.014. View

Xu L, Frederik P, Pirollo K, Tang W, Rait A, Huang W . Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery. Hum Gene Ther. 2002; 13(3):469-81. DOI: 10.1089/10430340252792594. View

Liu S, Wicha M . Targeting breast cancer stem cells. J Clin Oncol. 2010; 28(25):4006-12. PMC: 4872314. DOI: 10.1200/JCO.2009.27.5388. View

Belitsos P, Hildreth J, August J . Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression. J Immunol. 1990; 144(5):1661-70. View

Wong T, Liu X, Wong B, Ng R, Yuen A, Wei W . Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue. Clin Cancer Res. 2008; 14(9):2588-92. DOI: 10.1158/1078-0432.CCR-07-0666. View

10.

Polytarchou C, Iliopoulos D, Struhl K . An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci U S A. 2012; 109(36):14470-5. PMC: 3437881. DOI: 10.1073/pnas.1212811109. View

11.

Hu Y, Smyth G . ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009; 347(1-2):70-8. DOI: 10.1016/j.jim.2009.06.008. View

12.

Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J . Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 2009; 7(6):e1000121. PMC: 2683567. DOI: 10.1371/journal.pbio.1000121. View

13.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C . let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6):1109-23. DOI: 10.1016/j.cell.2007.10.054. View

14.

Nam E, Yoon H, Kim S, Kim H, Kim Y, Kim J . MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008; 14(9):2690-5. DOI: 10.1158/1078-0432.CCR-07-1731. View

15.

Xu L, Tang W, Huang C, Alexander W, Xiang L, Pirollo K . Systemic p53 gene therapy of cancer with immunolipoplexes targeted by anti-transferrin receptor scFv. Mol Med. 2001; 7(10):723-34. PMC: 1949994. View

16.

Griffin C, Curtis C, Davis R, Muthukumar V, Magnuson T . The chromatin-remodeling enzyme BRG1 modulates vascular Wnt signaling at two levels. Proc Natl Acad Sci U S A. 2011; 108(6):2282-7. PMC: 3038709. DOI: 10.1073/pnas.1013751108. View

17.

Park J, Venteicher A, Hong J, Choi J, Jun S, Shkreli M . Telomerase modulates Wnt signalling by association with target gene chromatin. Nature. 2009; 460(7251):66-72. PMC: 4349391. DOI: 10.1038/nature08137. View

18.

Hatfield S, Ruohola-Baker H . microRNA and stem cell function. Cell Tissue Res. 2007; 331(1):57-66. PMC: 2925125. DOI: 10.1007/s00441-007-0530-3. View

19.

Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

20.

Sheu J, Choi J, Yildiz I, Tsai F, Shaul Y, Wang T . The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1. Cancer Res. 2008; 68(11):4050-7. PMC: 2628471. DOI: 10.1158/0008-5472.CAN-07-3240. View