MAP3K3

Abstract: Background Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. Here in we determined the clinical significance of MEKK3 in ESCC.

Abstract: 17beta-estradiol (betaE(2)) is an effective neuroprotectant against hydrogen peroxide (H(2)O(2))-induced retinal neuronal cell death and light-induced photoreceptor degeneration. Muller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of betaE(2) on human Muller cells is unclear. In this study, the effects of betaE(2) on human Muller cell survival and gene expression were examined. Our data revealed that betaE(2) is able to increase human Muller cell viability after exposure to H(2)O(2) through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Muller cells 6 h after betaE(2) treatment. Four of the betaE(2)-responsive genes [thrombospondin 1 (TSP1), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium-activated potassium channel beta2 subunit (KCNMB2), and SRY (sex-determining region Y)-box 11 (SOX11)] were validated by both real-time qRT-PCR and semi-quantitative RT-PCR. Interestingly, exposure of human Muller cells to betaE(2) increased pigment epithelium-derived factor (PEDF) gene expression as measured by both RT-PCR and real time qRT-PCR. Our data demonstrate, for the first time, that betaE(2) protects cultured human Muller cells against H(2)O(2)-induced cell death through the inhibition of apoptosis. This protective effect may operate through regulation of genes, such as TSP1, MAP3K3, SOX11, TSP1, and PEDF, and may in turn exert an important role in protecting retinal neurons.

Abstract: MicroRNAs (miRNAs) are short non-coding RNAs, which generally regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR-505 in non-small cell lung cancer (NSCLC) cells was investigated. miR-505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase-quantitative polymerase chain reaction detection, it was demonstrated that miR-505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor-Node-Metastasis stage and distant metastasis in patients with NSCLC. Functional studies revealed that miR-505 inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition progress in vitro and tumor growth in vivo. Mechanically, mitogen-activated protein kinase kinase kinase 3 (MAP3K3) was identified as a direct target of miR-505 by binding to its 3′untranslated region and demonstrated to mediate the tumor suppressor roles of miR-505 in NSCLC cells. The effect of miR-505 on the activation of AKT/nuclear factor-κB (NFκB) pathway, which was downstream targets of MAP3K3, was further analyzed by western blot analysis and immunofluorescence analyses. The data demonstrated the inhibition of the AKT/NFκB pathway upon overexpressing miR-505 and the activation of AKT/NFκB pathway upon silencing miR-505. Collectively, the data revealed the novel role and target of miR-505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications.

Abstract: MicroRNA‑708‑5p (miR‑708‑5p) and epithelial‑​to‑mesenchymal transition (EMT) have been widely identified to contribute to the pathogenesis and progression of multiple cancers. However, the connection between miR‑708‑5p and EMT has not been sufficiently clarified. Therefore, our research aimed to investigate the impact of miR‑708‑5p on EMT and the metastasis of osteosarcoma (OS). We first analyzed the differentially expressed microRNAs (DEmiRNAs) from the GSE70367 dataset. We found that the expression of miR‑708‑5p was lower in OS cells. Overexpression of miR‑708‑5p was able to impair the migration and invasion of OS cells. Moreover, miR‑708‑5p inhibited EMT of OS cells MG63 and SaOS‑2, wherein E‑cadherin was increased, and N‑cadherin, vimentin, and Snail were decreased. Semaphorin 4C (SEMA4C), mitogen‑activated protein kinase kinase kinase 3 (MAP3K3), and zinc finger E‑box‑binding homeobox 1 (ZEB1) were predicted as target genes of miR‑708‑5p by bioinformatics method. Only ZEB1, one of the EMT‑inducing transcription factors, was validated as the direct target gene of miR‑708‑5p in OS cells through dual‑luciferase reporter assay and Western blot analysis. Knockdown of ZEB1 was found to inhibit the metastasis of MG63 and SaOS‑2 cells, whereas ZEB1 over-expression promoted their metastasis. In summary, miR‑708‑5p impaired the metastasis and EMT of OS, which was found to be mediated by inhibition of ZEB1.