MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression

  • Authors:
    • Rui Han
    • Jing Zhao
    • Lingeng Lu
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  • Published online on: March 18, 2020     https://doi.org/10.3892/or.2020.7549
  • Pages: 2062-2072
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Abstract

Breast cancer is the most common cancer type and the leading cause of cancer‑associated mortality in women across the majority of countries. In general, the incidence of breast cancer has been decreasing in developed countries over the previous 20 years, while it has increased in the other areas, such as the Asian‑Pacific region. MicroRNA‑34a (miR‑34a) targets stem cell‑associated transcription factors E2F1/E2F3, and may have clinical relevance in breast cancer. The present study aimed to investigate the association between miR‑34a/E2F1/E2F3 and patient survival in breast cancer, as well as the underlying molecular mechanism of miR‑34a in suppressing factors associated with tumor aggressiveness in vitro. Kaplan‑Meier survival curves were constructed and a meta‑analysis was performed to analyze the association of miR‑34a, E2F1 and E2F3 expression and overall survival in breast cancer, and the differential expression levels of E2F1 and E2F3 between breast cancer and normal breast tissues was assessed using publicly accessed datasets. Then 2D and 3D experiments on cell cultures were performed in vitro on both T‑47D and MDA‑MB‑231 cells to investigate the cancer biology of miR‑34a and its effect on E2F1 and E2F3 expression using reverse transcription‑quantitative PCR. Then, caspase‑3 (CASP3) activity was measured using a CaspACE™ assay system. E2F1 and E2F3 expression levels were upregulated in breast cancer, compared with normal breast tissues. Both high miR‑34a, and low E2F1 and E2F3 mRNA levels were positively associated with longer survival times in patients with breast cancer. The in vitro 2D and 3D cell experiments revealed that overexpression of miR‑34a significantly downregulated the expression of E2F1 and E2F3, and increased CASP3 activity in both T‑47D and MDA‑MB‑231 cells, and that miR‑34a treatment inhibited tumor cell proliferation, migration and invasiveness, as well as 3D spheroid formation. Thus, miR‑34a influences the aggressiveness of breast cancer and patient survival, and is a potential therapeutic tool in the clinical management of breast cancer.
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June-2020
Volume 43 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Han R, Zhao J and Lu L: MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression. Oncol Rep 43: 2062-2072, 2020
APA
Han, R., Zhao, J., & Lu, L. (2020). MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression. Oncology Reports, 43, 2062-2072. https://doi.org/10.3892/or.2020.7549
MLA
Han, R., Zhao, J., Lu, L."MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression". Oncology Reports 43.6 (2020): 2062-2072.
Chicago
Han, R., Zhao, J., Lu, L."MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression". Oncology Reports 43, no. 6 (2020): 2062-2072. https://doi.org/10.3892/or.2020.7549