MicroRNA‑143 targets CD44 to inhibit breast cancer progression and stem cell-like properties

Yang,Zhuangqing; Chen,Dedian; Nie,Jianyun; Zhou,Shaoqiang; Wang,Jiankui; Tang,Qi; Yang,Xiaojuan

doi:10.3892/mmr.2016.5194

MicroRNA‑143 targets CD44 to inhibit breast cancer progression and stem cell-like properties

Authors:
- Zhuangqing Yang
- Dedian Chen
- Jianyun Nie
- Shaoqiang Zhou
- Jiankui Wang
- Qi Tang
- Xiaojuan Yang
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Affiliations: Department of Mammary Glands, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, Yunnan 650118, P.R. China
Published online on: April 27, 2016 https://doi.org/10.3892/mmr.2016.5194
Pages: 5193-5199

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Abstract

CD44 is closely linked to breast cancer progression; however, the regulatory functions of microRNAs (miRs) in breast cancer have yet to be fully elucidated. In order to investigate the regulation of CD44 by miRs in breast cancer, the present study isolated CD44+ and CD44- breast cancer cells by flow cytometry, revealing that CD44+ cells were enriched in transplanted compared with those in primary breast cancers, and that their proliferation and stem-cell sphere formation ability were enhanced. A miRNA array assay indicated that miR-143 expression in CD44+ breast cancer cells was lower than that in CD44- cells. Furthermore, miR-143 was decreased in breast cancer tissues and cell lines compared with that in normal tissues and cells. Restoration of miR-143 expression in CD44+ breast cancer cells inhibited their proliferation and sphere formation. A luciferase reporter assay demonstrated that miR-143 directly tartgeted the 3'-untranslated region of CD44. In addition, miR-143 inhibited metastasis-associated features in breast cancer and reduced tumor growth in a mouse model of breast cancer. In conclusion, the results of the present study demonstrated that miR-143 inhibited the progression and stem-cell properties of breast cancer cells by targeting CD44.

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1	Kasai T, Chen L, Mizutani A, Kudoh T, Murakami H, Fu L and Seno M: Cancer stem cells converted from pluripotent stem cells and the cancerous niche. J Stem Cells Regen Med. 10:2–7. 2014.PubMed/NCBI
2	Visvader JE and Stingl J: Mammary stem cells and the differentiation hierarchy: Current status and perspectives. Genes Dev. 28:1143–1158. 2014. View Article : Google Scholar : PubMed/NCBI
3	Geng SQ, Alexandrou AT and Li JJ: Breast cancer stem cells: Multiple capacities in tumor metastasis. Cancer Lett. 349:1–7. 2014. View Article : Google Scholar : PubMed/NCBI
4	Fu N, Lindeman GJ and Visvader JE: The mammary stem cell hierarchy. Curr Top Dev Biol. 107:133–160. 2014. View Article : Google Scholar : PubMed/NCBI
5	Steinestel K, Eder S, Schrader AJ and Steinestel J: Clinical significance of epithelial-mesenchymal transition. Clin Transl Med. 3:172014. View Article : Google Scholar : PubMed/NCBI
6	Puisieux A, Brabletz T and Caramel J: Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 16:488–494. 2014. View Article : Google Scholar : PubMed/NCBI
7	Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI
8	Hao J, Zhang Y, Deng M, Ye R, Zhao S, Wang Y, Li J and Zhao Z: MicroRNA control of epithelial-mesenchymal transition in cancer stem cells. Int J Cancer. 135:1019–1027. 2014. View Article : Google Scholar : PubMed/NCBI
9	Vislovukh A, Vargas TR, Polesskaya A and Groisman I: Role of 3′-untranslated region translational control in cancer development, diagnostics and treatment. World J Biol Chem. 5:40–57. 2014. View Article : Google Scholar : PubMed/NCBI
10	van Rooij E and Kauppinen S: Development of microRNA therapeutics is coming of age. EMBO Mol Med. 6:851–864. 2014. View Article : Google Scholar : PubMed/NCBI
11	Yan X, Chen X, Liang H, Deng T, Chen W, Zhang S, Liu M, Gao X, Liu Y, Zhao C, et al: MiR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Mol Cancer. 13:2202014. View Article : Google Scholar : PubMed/NCBI
12	Ng EK, Li R, Shin VY, Siu JM, Ma ES and Kwong A: MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol. 35:2591–2598. 2014. View Article : Google Scholar
13	Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, Li B, Li Y, Li D, Wang ED and Liu MF: A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 31:1985–1998. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yu X, Zhang X, Dhakal IB, Beggs M, Kadlubar S and Luo D: Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells. BMC Cancer. 12:292012. View Article : Google Scholar : PubMed/NCBI
15	Xia H, Sun S, Wang B, Wang T, Liang C, Li G, Huang C, Qi D and Chu X: MiR-143 inhibits NSCLC cell growth and metastasis by targeting Limk1. Int J Mol Sci. 15:11973–11983. 2014. View Article : Google Scholar : PubMed/NCBI
16	Li R, Zhang L, Jia L, Duan Y, Li Y, Wang J, Bao L and Sha N: MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma. PLoS One. 9:e948552014. View Article : Google Scholar : PubMed/NCBI
17	Wu XL, Cheng B, Li PY, Huang HJ, Zhao Q, Dan ZL, Tian DA and Zhang P: MicroRNA-143 suppresses gastric cancer cell growth and induces apoptosis by targeting COX-2. World J Gastroenterol. 19:7758–7765. 2013. View Article : Google Scholar
18	Zhang N, Su Y and Xu L: Targeting PKCε by miR-143 regulates cell apoptosis in lung cancer. FEBS Lett. 587:3661–3667. 2013. View Article : Google Scholar : PubMed/NCBI
19	Zhang Y, Wang Z, Chen M, Peng L, Wang X, Ma Q, Ma F and Jiang B: MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer. Mol Cancer. 11:232012. View Article : Google Scholar : PubMed/NCBI
20	Xu B, Niu X, Zhang X, Tao J, Wu D, Wang Z, Li P, Zhang W, Wu H, Feng N, et al: MiR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS. Mol Cell Biochem. 350:207–213. 2011. View Article : Google Scholar : PubMed/NCBI