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KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia

  • Authors:
    • Hyun-Jung Ahn
    • Byul Moon
    • Mijin Park
    • Jung-Ae Kim

  • View Affiliations

  • Published online on: October 7, 2020     https://doi.org/10.3892/ol.2020.12199
  • Article Number: 335

  • Copyright: © Ahn et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxygen deprivation (hypoxia), which frequently occurs in the tumour microenvironment, is a strong driver of the phenotypic transition of cancer cells. An increase in metastatic potential such as cell invasion is a well‑known phenotypical change induced in hypoxia. The present study demonstrated that lysine demethylase 3A (KDM3A), a Jumonji C domain‑containing KDM, is involved in the hypoxia‑induced invasion of MCF7 breast cancer cells. KDM3A depletion inhibits the induction of cell invasion without affecting MCF7 cell survival rate or proliferation under hypoxic conditions, whereas KDM3A overexpression enhances MCF7 cell invasion even under normoxic conditions. KDM3A suppresses E‑cadherin expression, which is associated with epithelial‑to‑mesenchymal transition (EMT)‑mediated cell invasion in hypoxia. In addition, KDM3A promotes the expression of Slug, an EMT transcription factor that negatively regulates E‑cadherin expression. Consistent with this finding, the removal of the repressive transcription marker, dimethylated histone H3 at lysine 9 from the Slug promoter is dependent on hypoxia‑induced recruitment of KDM3A. Collectively, the results of the present study suggest that KDM3A is a crucial transcriptional coactivator of Slug expression to induce MCF7 breast cancer cell invasion in hypoxia, and that inhibition of KDM3A may efficaciously prevent metastatic cancer development.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Source Normalized Impact per Paper (SNIP): 0.574
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Spandidos Publications style
Ahn H, Moon B, Park M and Kim J: KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia. Oncol Lett 20: 335, 2020.
APA
Ahn, H., Moon, B., Park, M., & Kim, J. (2020). KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia. Oncology Letters, 20, 335. https://doi.org/10.3892/ol.2020.12199
MLA
Ahn, H., Moon, B., Park, M., Kim, J."KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia". Oncology Letters 20.6 (2020): 335.
Chicago
Ahn, H., Moon, B., Park, M., Kim, J."KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia". Oncology Letters 20, no. 6 (2020): 335. https://doi.org/10.3892/ol.2020.12199