Open Access

Epigenetically altered miR‑193a‑3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7

  • Authors:
    • Yiyin Tang
    • Siyuan Yang
    • Maohua Wang
    • Dequan Liu
    • Yang Liu
    • Ying Zhang
    • Qian Zhang
  • View Affiliations

  • Published online on: April 15, 2019     https://doi.org/10.3892/ijmm.2019.4167
  • Pages: 2352-2360
  • Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging evidence has demonstrated that microRNAs (miRNAs/miRs) have various biological functions in the development of human epidermal growth factor receptor 2 (HER2) positive breast cancer. The aim of the present study is to reveal the mechanism of miR‑193a‑3p inhibiting the progress of HER2 positive breast cancer. The expression of miR‑193a‑3p was evaluated by quantitative polymerase chain reaction (PCR). The methylation status of miR‑193a‑3p was evaluated by PCR and pyrosequencing analysis. Overexpression of miR‑193a‑3p and growth factor receptor bound protein 7 (GRB7) combined with in vitro tumorigenic assays were conducted to determine the carcinostatic capacities of miR‑193a‑3p in HER2 positive breast cancer cells. The association between miR‑193a‑3p and GRB7 was determined by luciferase reporter assay. Protein level was evaluated using western blot analysis. miR‑193a‑3p was downregulated in HER2 positive breast cancer cells and clinical tissues. Methylation‑mediated silencing led to decreased expression of miR‑193a‑3p in HER2 positive breast cancer. Overexpression of miR‑193a‑3p could inhibit proliferation, migration and invasion of breast cancer cells. Overexpression of GRB7 could abolish this effect. miR‑193a‑3p could directly target the 3' untranslated region of GRB7. miR‑193a‑3p could directly or indirectly target extracellular signal‑regulated kinase 1/2 (ERK1/2) and forkhead box M1 (FOXM1) signaling. In conclusion, it was identified that silencing of miR‑193a‑3p through hypermethylation can promote HER2 positive breast cancer progress by targeting GRB7, ERK1/2 and FOXM1 signaling. The function of miR‑193a‑3p in HER2 positive breast cancer implicates its potential application in therapy.
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June-2019
Volume 43 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tang Y, Yang S, Wang M, Liu D, Liu Y, Zhang Y and Zhang Q: Epigenetically altered miR‑193a‑3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7. Int J Mol Med 43: 2352-2360, 2019.
APA
Tang, Y., Yang, S., Wang, M., Liu, D., Liu, Y., Zhang, Y., & Zhang, Q. (2019). Epigenetically altered miR‑193a‑3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7. International Journal of Molecular Medicine, 43, 2352-2360. https://doi.org/10.3892/ijmm.2019.4167
MLA
Tang, Y., Yang, S., Wang, M., Liu, D., Liu, Y., Zhang, Y., Zhang, Q."Epigenetically altered miR‑193a‑3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7". International Journal of Molecular Medicine 43.6 (2019): 2352-2360.
Chicago
Tang, Y., Yang, S., Wang, M., Liu, D., Liu, Y., Zhang, Y., Zhang, Q."Epigenetically altered miR‑193a‑3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7". International Journal of Molecular Medicine 43, no. 6 (2019): 2352-2360. https://doi.org/10.3892/ijmm.2019.4167