miR-515-5p controls cancer cell migration through MARK4 regulation

Pardo, Olivier E, Castellano, Leandro, Munro, Catriona E, Hu, Yili, Mauri, Francesco, Krell, Jonathan, Lara, Romain, Pinho, Filipa G, Choudhury, Thameenah, Frampton, Adam E, Pellegrino, Loredana, Pshezhetskiy, Dmitry, Wang, Yulan, Waxman, Jonathan, Seckl, Michael J and Stebbing, Justin (2016) miR-515-5p controls cancer cell migration through MARK4 regulation. EMBO reports, 17 (4). pp. 570-584. ISSN 1469-3178

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Abstract

Here, we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq analyses of both oestrogen receptor receptor-positive and receptor-negative breast cancer cells overexpressing miR-515-5p reveal down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3' UTR interaction and that MARK4 knock-down mimics the effect of miR-515-5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR-515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation. Furthermore, miR-515-5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in cell migration and metastasis across two common cancers.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Leandro Castellano
Date Deposited: 15 Jun 2018 10:41
Last Modified: 15 Jun 2018 10:41
URI: http://sro.sussex.ac.uk/id/eprint/76522

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