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

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Authors

  • Olivier E Pardo
  • Leandro Castellano
  • Catriona E Munro
  • Yili Hu
  • Francesco Mauri
  • Jonathan Krell
  • Romain Lara
  • Filipa G Pinho
  • Thameenah Choudhury
  • Adam E Frampton
  • Loredana Pellegrino
  • Dmitry Pshezhetskiy
  • Yulan Wang
  • Jonathan Waxman
  • Michael J Seckl
  • Justin Stebbing

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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.

Details

Original languageEnglish
Pages (from-to)570-584
Number of pages15
JournalEMBO reports
Volume17
Issue number4
Early online date10 Feb 2016
DOIs
StatePublished - 1 Apr 2016
Peer-reviewedYes

Keywords

    Research areas

  • Breast Cancer, Lung Cancer, MicroRNAs, Microtubule Affinity‐Regulating Kinase 4, MiR‐515‐5p

Bibliographic note

© 2016 The Authors. Published under the terms of the CC BY 4.0 license.

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