title: miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1.
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.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Shyamasundar
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Jia Pei
authors.initials: JP
authors.lastname: Lim
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Boon Huat
authors.initials: BH
authors.lastname: Bay
mesh_terms: D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human