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

Breast Cancer. 2020 Jan;27(1):147-158. doi: 10.1007/s12282-019-01002-0. Epub 2019 Aug 13.


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; CCK-8; E2F2; Stemness; miR-638.

MeSH terms

  • Animals
  • Binding Sites
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Cell Self Renewal
  • E2F2 Transcription Factor / genetics*
  • E2F2 Transcription Factor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / metabolism
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • RNA, Small Interfering


  • CD44 protein, human
  • E2F2 Transcription Factor
  • E2F2 protein, human
  • Hyaluronan Receptors
  • MIRN638 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering