Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer

  • Authors:
    • Wentong Li
    • Chuanliang Liu
    • Chunling Zhao
    • Limin Zhai
    • Shijun Lv
  • View Affiliations

  • Published online on: January 5, 2016     https://doi.org/10.3892/ijo.2016.3319
  • Pages: 1155-1164
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Abstract

Integrins are adhesion receptors involved in bidirectional signaling and are crucial for various cellular responses during normal homeostasis and pathological conditions, such as cancer progression and metastasis. In the present study, we demonstrated that blockage of β3 integrin-mediated cell- extracellular matrix interactions restrained triple-negative breast cancer (TNBC) growth, and elevated β3 integrin can trigger the rewiring of Erk/Ets-1 signaling pathways, thereby enhancing cell growth and invasion. Ectopic expression of miRNA has been implicated in the deregulation of integrin expression and activity, blocking of cancer tumor development and progression, and acquisition of metastatic phenotype. miR-30a-5p expression has been implicated in the progression of breast cancer. Overexpression of miR-30a-5p suppressed the proliferation, migration and invasion of breast cancer cells. On the contrary, inhibition of miR-30a-5p promoted the proliferation, migration, and invasion of TNBC cells by suppressing the expression of ERK/Ets-1 signal. An inverse correlation was found between the mRNA expressions of miR-30a-5p and β3 integrin in TNBC samples. Furthermore, bioinformatics analysis revealed the putative miR-30 binding sites in the 3'-UTR of β3 integrin. Results of luciferase assay revealed a strong repression of luciferase activity after transfection with miR‑30a-5p and wild-type 3'-UTR of β3 integrin. In TNBC cells, miR-30a-5p promoted an epithelial phenotype and suppressed invasion by specifically targeting β3 integrin subunit to subsequently interdict the β3 integrin/Erk/Ets-1 network.
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March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Li, W., Liu, C., Zhao, C., Zhai, L., & Lv, S. (2016). Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer. International Journal of Oncology, 48, 1155-1164. https://doi.org/10.3892/ijo.2016.3319
MLA
Li, W., Liu, C., Zhao, C., Zhai, L., Lv, S."Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer". International Journal of Oncology 48.3 (2016): 1155-1164.
Chicago
Li, W., Liu, C., Zhao, C., Zhai, L., Lv, S."Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer". International Journal of Oncology 48, no. 3 (2016): 1155-1164. https://doi.org/10.3892/ijo.2016.3319