miR-449a targets Flot2 and inhibits gastric cancer invasion by inhibiting TGF-β-mediated EMT

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.

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

“…Several lines of evidence have implicated that SBD exerts a strong activity of anti-tumour, anti-oxidative stress and anti-inflammation [10][11][12]. Recent studies mainly focused on its anti-tumour effects which have been reported in many kinds of cancers [13][14][15]. Besides, SBD had prominent antioxidant activity and free radical-scavenging property [19].…”

“…Scutellaria barbata D. Don (SBD), also known as Ban-Zhi-Lian, is a perennial herb with multiple pharmacological effects, including anti-inflammation, anti-oxidation and anti-tumour activity [10][11][12]. It has been demonstrated that SBD has a strong inhibitory effect on numerous human cancers, such as lung cancer, hepatocellular carcinoma and skin cancer [13][14][15]. While the antioxidant effect of SBD has been widely accepted, its functional effects on neuronal oxidative injury have not been reported.…”

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

“…FLOT2 inhibits cell proliferation, migration and invasion of gastric cancer cells [25]. FLOT2 is up-regulated in gastric cancer and miR-449a reduces cell invasion by inhibiting the expression of Flot2 via TGFb-mediated EMT [26]. FLOT2 is highly expressed in oral squamous cell carcinoma [27], nasopharyngeal carcinoma [28] and non-small cell lung cancer [29].…”

Flotillin membrane domains in cancer

“…Flotillin 1 is a microRNA-124 target in breast tumors [16], and flotillin 2 is a microRNA-485-5p target in non-small-cell lung cancer [62]. In gastric cancer, microRNA-485-5p targets flotillin 1 and microRNA-449a flotillin 2 [63,64]. Gene amplification also might increase flotillin expression level.…”