Abstract
BackgroundEpithelial ovarian cancer (EOC) is still a major gynecologic problem with poor 5 year survival rate due to distance metastases, despite routine surgery and chemotherapy. The precise underlying molecular mechanisms that trigger EOC migration and invasion are unclear. Recent studies suggest that the expression of microRNAs is widely dysregulated in ovarian cancer; and that they have evolved into tumorigenic processes, including cell proliferation, apoptosis and motility.MethodsThe expression of miR-124 was assessed in clinical ovarian cancer specimens and cell lines using miRNA qRTPCR. The function of miR-124 on cell migration and invasion was confirmed in vitro through wound healing assay and transwell assay. Luciferase reporter assay was used to confirm target associations.ResultsWe showed that miR-124 is down-regulated in ovarian cancer specimens as well as in cell lines; and that low-level expression of miR-124 is much lower in highly metastatic ovarian cancer cells and tissues. Meantime, overexpression of miR-124 dramatically inhibits the motility of ovarian cancer cells in vitro and substantially suppresses the protein expression of SphK1, reported as an invasion and metastasis-related gene in human cancers, whose expression is markedly increased in both ovarian cancer cell lines and clinical samples, particularly in two highly metastasis cells, SKOV3-ip and HO8910pm as well as metastatic ovarian tumor tissues. Furthermore, SphK1 is identified as a direct target of miR-124, and knock-down of SphK1 in ovarian cancer cells, SKOV3-ip and HO8910pm, could mimic the inhibition of migration and invasion by miR-124, while re-introduction of SphK1 abrogates the suppression of motility and invasiveness induced by miR-124 in both cell lines.ConclusionsOur studies suggest a protective role of miR-124 in inhibition of migration and invasion in the molecular etiology of ovarian cancer, and a potentially novel application of miR-124 in the regulation of migration and invasion in EOC.
Highlights
Epithelial ovarian cancer (EOC) is still a major gynecologic problem with poor 5 year survival rate due to distance metastases, despite routine surgery and chemotherapy
To verify the target involved in progression of ovarian cancer, we searched putative target genes via miRanda and TargetScan and we focused on Sphingosine kinase 1 (SphK1) because of its rank and function associated with migration and invasion, the ectopic expression of miR-124 substantially decreased the expression of SphK1 in both SKOV3-ip and HO8910pm ovarian cancer cells assessed by western blot assay (Figure 2D and Additional file 2C), real-time PCR analysis did not show obvious changes in mRNA expression of SphK1 (Additional file 2B)
We showed that miR-124 inhibited EOC cell migration and invasion, which may be involved in the development of ovarian cancer metastasis
Summary
Epithelial ovarian cancer (EOC) is still a major gynecologic problem with poor 5 year survival rate due to distance metastases, despite routine surgery and chemotherapy. Recent studies suggest that the expression of microRNAs is widely dysregulated in ovarian cancer; and that they have evolved into tumorigenic processes, including cell proliferation, apoptosis and motility. More and more studies have reported a functional contribution of specific miRNAs in diverse biological processes [6,7,8], including deregulation of miRNAs. Ovarian cancer, one of the most common causes of death in women worldwide, is still a major problem in China over the past few decades [11,12,13] with high mortality, which is mainly due to the fact that more than 70% of patients are in late-stage, with distant metastases at the time of diagnosis [2,9]. The expression level and the possible role of miR-124 in ovarian cancer remain to be explored
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