miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1

Shyamasundar,Sukanya; Lim,Jia Pei; Bay,Boon Huat

doi:10.3892/ijo.2016.3761

miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1

Authors:
- Sukanya Shyamasundar
- Jia Pei Lim
- Boon Huat Bay
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Affiliations: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore
Published online on: November 7, 2016 https://doi.org/10.3892/ijo.2016.3761
Pages: 2629-2636

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Abstract

Despite advances in treatment, the highly metastatic nature of breast tumors has given rise to the urgent need for development of novel therapeutic and prognostic markers. miR-93 is known to regulate the epithelial to mesenchymal transition process and to influence metastatic spread in breast carcinoma, although the exact mechanism(s)/genes involved remain unknown. In the present study, we examined the role of miR-93 in MDA-MB-231 breast cancer cells. Overexpression of mature miR-93-5p in MDA-MB-231 cells decreased cell migratory capability and invasive potential, as well as increased adhesion. In contrast, inhibition of miR-93 induced the opposite effects. miRNA-mRNA target prediction (TargetScan) identified WNK lysine deficient protein kinase 1 (WNK1), which is known to interact with diverse signaling pathways and regulate cell proliferation, survival, angiogenesis and metastasis, as one of the potential targets of miR-93. Furthermore, we showed by luciferase assay that WNK1 is a putative miR-93 target. siRNA mediated silencing of WNK1 also decreased the invasive ability of the cells, suggesting that the effects of miR-93 may be attributed at least in part to decreased WNK1 expression. Further in vivo studies are required to ascertain the miR-93-WNK1-metastasis cascade, that has potential implications in breast cancer therapy.

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