MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway

Abstract

Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.

MicroRNA-100 suppresses human gastric cancer cell proliferation by targeting CXCR7

“…Collectively, we deducted that miR-100 expression could suppress the cell proliferation in GC. Numerous miR-100 target genes have been identified in previous literatures (17,19,25,29,30). Using the bioinformatical tools, we found the 3'-UTR of CXCR7 has a putative binding site for miR-100 and the luciferase reporter assay confirmed CXCR7 is a direct target of miR-100.…”

“…However, the biological function of miR-100 in GC is still unknown. Previous studies demonstrated that miR-100 could inhibit cell proliferation, migration, and differentiation in human cancers (19,(29)(30). Therefore, the effect of miR-100 on cell proliferation was evaluated in vitro.…”

“…Therefore, in this present study, we aimed to identify new miRNA biomarker that could be used as predictor for the overall survival of GC patients and also with the hope to reveal the underlying mechanism of how miRNA participated in the development of GC. miR-100 has been found aberrant expressed in several human cancers but its role in tumorigenesis is still controversial (16)(17)(18)(19)(20). The reason for that might be it can regulate different downstream target genes and therefore it can have different and even opposite functions in tumors.…”

“…Extensive studies have been performed to evaluate the role of miR-100 in tumors but the results seemed to be controversial. For example, miR-100 was found to acting as tumor suppressor by deregulation its target genes in hepatocellular carcinoma (17), epithelial ovarian cancer (18), and breast cancer (19). However, miR-100 was also found to acting as oncogene in renal cell carcinoma (20) and acute myeloid leukemia (16).…”

WNT5A and Its Receptors in the Bone-Cancer Dialogue

“…However, some receptors, including ROR2, have been shown to activate both canonical and noncanonical Wnt signaling in breast cancer cells. (81) In addition, miRNAs such as miR-100 negatively correlate with FZD8 expression and decrease the invasive capacity of tumor cells by reducing the activation of canonical Wnt signaling (84) (Fig. 2B, label 5).…”