Abstract
BackgroundFlot2, a highly conserved protein of the SPFH domain containing proteins family, has recently been identified as oncogene to be involved in the tumorigenesis and metastasis of several cancers including gastric cancer. However, the underlying molecular mechanism of Flot2 in gastric cancer (GC) is largely unknown.MethodsqRT-PCR and western blot was performed to detect miR-449a and Flot2 expression in GC cell lines and Normal human gastric epithelial cells. Then, luciferase reporter assay was used to elucidate whether Flot2 is a target gene of miR-449a. Finally, the roles and mechanism of miR-449a in regulation of tumor invasion were further investigated.ResultsIn this study, miR-449a expression was downregulated and Flot2 was upregulated in all GC cell lines as compared with that in GES-1. luciferase reporter assay identified Flot2 as a novel direct target of miR-449a. miR-449a regulated GC cell invasion by suppressing Flot2 expression. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers showed that miR-449a reduced the expression of mesenchymal markers (vimentin and N-cadherin) and induced the expression of epithelial marker (E-cadherin), which was consistent with silenced Flot2. Moreover, Flot2 is necessary for TGF-β-induced EMT in GC cells.ConclusionsOur results demonstrated that miR-449a suppressed Flot2 expression results in decreased cell invasion through repressing TGF-β-mediated-EMT, and provides a new theoretical basis to further investigate miR-449a-regulated Flot2 as a potential biomarker and a promising approach for GC treatment.
Highlights
Flot2, a highly conserved protein of the SPFH domain containing proteins family, has recently been identified as oncogene to be involved in the tumorigenesis and metastasis of several cancers including gastric cancer
The expression of miR-141 was reported to be significantly reduced in GC and was significantly correlated with a more aggressive phenotype of GC in patients [17]. miR-153, as an independent prognostic marker for predicting survival of gastric cancer patients, is downregulated in GC and promote gastric cancer cell migration and invasion, by inhibiting SNAI1-induced epithelial-mesenchymal transition (EMT) [18]. miR-449a was downregulated in gastric cancer cell lines and gastric cancer tissues [19, 20], and inhibits proliferation and induces apoptosis by directly repressing E2F3 [19]
Consistent with previous study [19], the miR-449a expression was downregulated in all GC cell lines as compared with that in GES-1 (Fig. 1a), indicating that miR-449a may function as a tumor suppressor in GC cells
Summary
A highly conserved protein of the SPFH domain containing proteins family, has recently been identified as oncogene to be involved in the tumorigenesis and metastasis of several cancers including gastric cancer. The underlying molecular mechanism of Flot in gastric cancer (GC) is largely unknown. It is essential to elucidate the molecular mechanisms of GC proliferation and metastasis, which will provide important insights and help us find new diagnostic and therapeutic approaches to this disease and improve the prognosis of GC patients. MiR-153, as an independent prognostic marker for predicting survival of gastric cancer patients, is downregulated in GC and promote gastric cancer cell migration and invasion, by inhibiting SNAI1-induced EMT [18]. MiR-449a was downregulated in gastric cancer cell lines and gastric cancer tissues [19, 20], and inhibits proliferation and induces apoptosis by directly repressing E2F3 [19]. The effects and mechanism of miR-449a on GC cell invasion remains unclear
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