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.

MicroRNA‐93‐5p expression in tumor tissue and its tumor suppressor function via targeting programmed death ligand‐1 in colorectal cancer

“…The results indicated that in SW480 cells, miR‐93‐5p regulated PD‐L1 specifically and negatively, which was previously found in pancreatic cancer (Cioffi et al, 2017); moreover, we also noted that transfection of miR‐93‐5p mimics decreased the level of PD‐L1, and this effect was abolished with the administration of inhibitors; in PD‐L1‐negative patients, miR‐93‐5p expression was significantly elevated, suggesting the key role of miR‐93‐5p targeting PD‐L1 . miR‐93‐5p, a member of the miR‐106b‐25 gene cluster located on chromosome 7q22, is not only an oncogene in many tumors (Li et al, 2018, 2019) but is also a tumor suppressor in certain tumors (Shyamasundar et al, 2016; Xiang et al, 2017). The results of this study suggested that miR‐93‐5p expression was downregulated in the tumor tissues and had a significant association with the major clinicopathological features and survival of patients.…”

A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis

“…Specifically, of the 13 miRNAs included in our signature, there is limited evidence regarding the role of hsa-miR-125-5p in breast cancer progression, while there is some evidence to suggest that miR-301-5p stimulates proliferation and invasion (26) and that hsa-miR-196-5p and hsa-miR-340-5p inhibit progression (27,28). For hsa-miR-30-5p, hsa-miR-130-5p, hsa-miR-93-5p, hsa-miR-503-5p, and hsa-miR-205-5p, there is conflicting evidence regarding their roles in breast cancer progression, with some reports suggesting functions that operate to increase the risk of progression and others suggesting the reverse (29)(30)(31)(32)(33)(34)(35). The apparently conflicting evidence regarding the roles of specific miRNAs in breast cancer prognosis is consistent with the observation that some miRNAs exert both oncogenic and tumor suppressive effects (36,37).…”

PDK1‑WNK1 signaling is affected by HBx and involved in the viability and metastasis of hepatic cells

“…WNK1 is the main downstream effector of the PDK1-associated pathway (16), which serves an important function in cell proliferation and migration (17). Previous studies demonstrated that WNK1 may also be an important kinase involved in various types of cancer (18)(19)(20)(21).…”