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

  • Qiu-Yan Lin
  • Jia-Qi Wang
  • Li-Li Wu
  • Wei-E Zheng
  • Pei-Rui ChenEmail author
Original Article
  • 32 Downloads

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.

Keywords

BCSCs miR-638 E2F2 Stemness CCK-8 

Notes

Author contributions

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

Compliance with ethical standards

Conflict of interest

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

Ethical approval

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

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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  • Qiu-Yan Lin
    • 1
  • Jia-Qi Wang
    • 1
  • Li-Li Wu
    • 1
  • Wei-E Zheng
    • 1
  • Pei-Rui Chen
    • 1
    Email author
  1. 1.Department of Medical OncologyRuian People’s HospitalWenzhouChina

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