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miR-638 represses the stem cell characteristics of breast cancer cells by targeting E2F2

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Abstract

Objective

The miR-638 acted as a tumor suppressor and E2F transcription factor 2 (E2F2) was a critical regulator in some cancers, while the role of them on stemness of breast cancer stem cells (BCSCs) was rarely detailed. Hence, we focused on exploring the effects of miR-638 and E2F2 on BCSCs stemness.

Methods

The proportion of CD24 −/CD44 + cells of BCSCs was detected by flow cytometry. The target relationship of miR-638 and E2F2 was explored using luciferase assays. The ability of self-renewal, proliferation, and invasion of BCSCs were determined by Mammosphere forming, Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. Xenograft tumor was established to detect the influence of miR-638 on tumor growth.

Results

miR-638 was down-regulated, while E2F2 was elevated in breast cancer. The E2F2 level was negatively correlated with miR-638. The BCSCs represented higher proportion of CD24 −/CD44 + cells and levels of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4). The miR-638 was down-regulated and E2F2 was increased in BCSCs. MiR-638 could target to E2F2 and decreased the level of E2F2 in BCSCs cells. Overexpression of miR-638 decreased the proportion of CD24 −/CD44 + cells and the levels of SOX2 and OCT4 by inhibiting E2F2. The overexpression of miR-638 also inhibited the abilities of self-renewal, proliferation, and invasion of BCSCs by inhibiting E2F2. The miR-638 overexpression inhibited the breast tumor growth.

Conclusion

MiR-638 represses the characteristics and behaviors of BCSCs by targeting E2F2. MiR-638 may be a potential target for breast cancer therapy.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Medical Oncology, Ruian People’s Hospital, Wansong Road No. 108, Wenzhou, 325200, Zhejiang, China

    Qiu-Yan Lin, Jia-Qi Wang, Li-Li Wu, Wei-E Zheng & Pei-Rui Chen

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  1. Qiu-Yan Lin
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  2. Jia-Qi Wang
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  3. Li-Li Wu
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  4. Wei-E Zheng
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  5. Pei-Rui Chen
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Contributions

QYL and PRC conceived and designed the experiments,JQW and LLW analyzed and interpreted the results of the experiments, WEZ performed the experiments.

Corresponding author

Correspondence to Pei-Rui Chen.

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The authors declare that they have no competing interests, and all authors should confirm its accuracy.

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The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfare Committee.

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Lin, QY., Wang, JQ., Wu, LL. et al. miR-638 represses the stem cell characteristics of breast cancer cells by targeting E2F2. Breast Cancer 27, 147–158 (2020). https://doi.org/10.1007/s12282-019-01002-0

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  • DOI: https://doi.org/10.1007/s12282-019-01002-0

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