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Cancers (Basel). 2020 Mar 26;12(4). doi: 10.3390/cancers12040795.

Tetraspanin CD9 is Regulated by miR-518f-5p and Functions in Breast Cell Migration and In Vivo Tumor Growth.

Cancers

Danielle R Bond, Richard Kahl, Joshua S Brzozowski, Helen Jankowski, Crystal Naudin, Mamta Pariyar, Kelly A Avery-Kiejda, Christopher J Scarlett, Claude Boucheix, William J Muller, Leonie K Ashman, Murray J Cairns, Séverine Roselli, Judith Weidenhofer

Affiliations

  1. School of Biomedical Science and Pharmacy, The University of Newcastle and Hunter Medical Research Institute (HMRI), Newcastle, NSW 2308, Australia.
  2. Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
  3. School of Environmental and Life Sciences, The University of Newcastle and Hunter Medical Research Institute (HMRI), Newcastle, NSW 2308, Australia.
  4. INSERM U935, Université Paris-Sud, Bâtiment Lavoisier, 14 Avenue Paul-Vaillant-Couturier, F-94800 Villejuif, France.
  5. Molecular Oncology Group, Department of Biochemistry, McGill University, Montreal, Quebec, H3A 1A3, Canada.
  6. Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW 2308, Australia.

PMID: 32224917 PMCID: PMC7226392 DOI: 10.3390/cancers12040795

Abstract

Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown. Therefore, this study aimed to elucidate the role of miR-518f-5p and the mechanisms responsible for decreased CD9 expression in breast cancer, as well as the role of CD9 in de novo tumor formation and metastasis. miR-518f-5p function was assessed using migration, adhesion, and proliferation assays. miR-518f-5p was overexpressed in breast cancer cell lines that displayed significantly lower CD9 expression as well as less endogenous CD9 3'UTR activity, as assessed using qPCR and dual luciferase assays. Transfection of miR-518f-5p significantly decreased CD9 protein expression and increased breast cell migration in vitro. Cd9 deletion in the MMTV/PyMT mouse model impaired tumor growth, but had no effect on tumor initiation or metastasis. Therefore, inhibition of miR-518f-5p may restore CD9 expression and aid in the treatment of breast cancer metastasis.

Keywords: CD9; breast cancer; miR-518f-5p; migration; regulation

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