Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC
NEOPLASMA
Authors: Zeng, C. X.; Tang, L. Y.; Xie, C. Y.; Li, F. X.; Zhao, J. Y.; Jiang, N.; Tong, Z.; Fu, S. B.; Wen, F. J.; Feng, W. S.
Abstract
The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated and significantly enhanced in hepatocellular carcinoma (HCC) tissues and cell lines compared to normal liver tissues and cell lines. MTT and colony formation assays demonstrated that EPS8L3 over-expression induces HCC cell proliferation and silencing reduces it. Further experiments illustrated that over-expressing EPS8L3 promotes p-AKT and Cyclin D1 expression, but inhibits the transcriptional activity of FOXO1. Colony formation assay also demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-over-expressing cells, while AKT restores the proliferation of EPS8L3-silenced cells. This suggests that EPS8L3 promotes proliferation by hyper-activating the AKT signaling pathway and subsequently inhibiting FOXO1 transcriptional activity. Our results provide a new view on EPS8L3 and human HCC progression and therefore EPS8L3 may prove a novel therapeutic target for HCC.
The arouser EPS8L3 Gene Is Critical for Normal Memory in Drosophila
PLOS ONE
Authors: LaFerriere, Holly; Ostrowski, Daniela; Guarnieri, Douglas J.; Zars, Troy
Abstract
The genetic mechanisms that influence memory formation and sensitivity to the effects of ethanol on behavior in Drosophila have some common elements. So far, these have centered on the cAMP/PKA signaling pathway, synapsin and fas2-dependent processes, pumilio-dependent regulators of translation, and a few other genes. However, there are several genes that are important for one or the other behaviors, suggesting that there is an incomplete overlap in the mechanisms that support memory and ethanol sensitive behaviors. The basis for this overlap is far from understood. We therefore examined memory in arouser (aru) mutant flies, which have recently been identified as having ethanol sensitivity deficits. The aru mutant flies showed memory deficits in both short-term place memory and olfactory memory tests. Flies with a revertant aru allele had wild-type levels of memory performance, arguing that the aru gene, encoding an EPS8L3 product, has a role in Drosophila memory formation. Furthermore, and interestingly, flies with the aru(8-128) insertion allele had deficits in only one of two genetic backgrounds in place and olfactory memory tests. Flies with an aru imprecise excision allele had deficits in tests of olfactory memory. Quantitative measurements of aru EPS8L3 mRNA expression levels correlate decreased expression with deficits in olfactory memory while over expression is correlated with place memory deficits. Thus, mutations of the aru EPS8L3 gene interact with the alleles of a particular genetic background to regulate arouser expression and reveals a role of this gene in memory.