Pellegrino, Loredana, Stebbing, Justin, Braga, Vania M, Frampton, Adam E, Jacob, Jimmy, Buluwela, Lakjaya, Jiao, Long R, Periyasamy, Manikandan, Madsen, Chris D, Caley, Matthew P, Ottaviani, Silvia, Roca-Alonso, Laura, El-Bahrawy, Mona, Coombes, R Charles, Krell, Jonathan and Castellano, Leandro (2013) miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts. Nucleic Acids Research, 41 (10). pp. 5400-5412. ISSN 1362-4962

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Abstract

Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Biochemistry
Depositing User:	Leandro Castellano
Date Deposited:	15 Jun 2018 12:32
Last Modified:	02 Jul 2019 15:30
URI:	http://sro.sussex.ac.uk/id/eprint/76534

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