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

• Type of Material: Article
• Authors: Danielle R Bond, The University of Newcastle and Hunter Medical Research Institute (HMRI); Richard Kahl, The University of Newcastle and Hunter Medical Research Institute (HMRI); Joshua S Brzozowski, The University of Newcastle and Hunter Medical Research Institute (HMRI); Helen Jankowski, The University of Newcastle and Hunter Medical Research Institute (HMRI); Crystal Naudin, Emory University; Mamta Pariyar, The University of Newcastle and Hunter Medical Research Institute (HMRI); Kelly A Avery-Kiejda, The University of Newcastle and Hunter Medical Research Institute (HMRI); Christopher J Scarlett, The University of Newcastle and Hunter Medical Research Institute (HMRI); Claude Boucheix, Université Paris-Sud, Bâtiment Lavoisier; William J Muller, McGill University; Leonie K Ashman, The University of Newcastle and Hunter Medical Research Institute (HMRI); Murray J Cairns, The University of Newcastle and Hunter Medical Research Institute (HMRI); Séverine Roselli, The University of Newcastle and Hunter Medical Research Institute (HMRI); Judith Weidenhofer, The University of Newcastle and Hunter Medical Research Institute (HMRI)
• Language: English
• Date: 2020-04-01
• Publisher: MDPI AG
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers12040795
• Title of Journal or Parent Work: Cancers
• Volume: 12
• Issue: 4
• Grant/Funding Information: K.A.K. is supported by the Cancer Institute NSW (Career Development Fellowship; CDF181205).; H.J. is funded by the Hunter Cancer Research Alliance.; The project was further funded by a Hunter Medical Research Institute project grant, donated by the Stroud Rodeo, and a University of Newcastle Faculty of Health pilot grant.; D.B. was supported by an Australian Postgraduate Award. S.R. was funded by the Cancer Institute NSW (Early Career Fellowship; 06/ECF/1/22)
• Keywords: breast cancer; migration; miR-518f-5p; regulation; CD9
• Research Categories: Health Sciences, Oncology; Chemistry, Biochemistry

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.