Here we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq
analyses of both estrogen receptor-positive and negative breast cancer cells overexpressing
miR-515-5p reveals 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 knockdown mimics the effect of miR-515-5p on breast and
lung cancer cell migration. MARK4 over-expression 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.