Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelial-mesenchymal transition (EMT) is an important step in cancer invasion. Metadherin (MTDH) contributes to EMT in several cancers, but the role and mechanism of MTDH in EMT-like process of glioma remain unknown. Here we demonstrate that MTDH was overexpressed in glioma tissues and cells and induced EMT-like change and invasion of glioma cells. Interestingly, MTDH could modulate the expression of a group of glioma-related miRNAs. In particular, MTDH upregulated miR-130b transcription via acting as a coactivator of NF-kB. MiR-130b promoted EMT-like change and invasion of glioma cells through targeting multiple EMT-related genes, including PTEN, PPP2CA and SMAD7. In addition, PTEN acted as the competing endogenous RNA (ceRNA) to affect PPP2CA and SMAD7 expression, and inhibited EMT-like change in glioma cells. Furthermore, miR-130b mediated EMT-like change induced by MTDH, and MTDH inhibited the expression levels of PTEN, PPP2CA and SMAD7. Taken together, we reveal a novel mechanism that MTDH induces EMT-like change and invasion of glioma via the regulation of miR-130b-ceRNAs, providing the first direct link between MTDH and miRNAs in cancer cells.
Background: Glioma is the primary cancer of the central nervous system, and defining the prognosis of glioma is of great significance in the clinical. The long noncoding RNAs (lncRNAs) emerge as important regulators of pathological processes. This study aimed to identify lncRNAs which could function as potential prognosis biomarkers of glioma.Material and Methods: Glioma RNA-seq data from TCGA and CGGA were analyzed to identify neoplasm grade associated lncRNAs by DEseq. 2R and weighted gene co-expression network analysis. Consensus module genes were analyzed in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway to predict lncRNAs biological functions. Then neutrophil immune estimations were analyzed by Tumor Immune Estimation Resource. Transcrption factors of these lncRNAs were predicted by PROMO. Overall survival and receiver operating characteristic (ROC) analyses were applied to test the accuracy of predicted lncRNAs as the markers of prognosis.
Results:We identified four lncRNAs most correlated with both higher neoplasm grade and worse prognosis, including AC064875.2, HOTAIRM1, LINC00908, and RP11-84A19.3. Neutrophil-mediated immunity and cell adhesion junction were considered as the main biological functions of these lncRNAs. In addition, the correlation of these four lncRNAs with glioma prognosis was validated. Conclusion: Neutrophil immune infiltration is implicated in higher neoplasm grade and worse prognosis of glioma. AC064875.2, HOTAIRM1, LINC00908, and RP11-84A19.3 may serve as potential prognosis biomarkers of glioma. K E Y W O R D S glioma, lncRNA, neutrophil, prognosis F I G U R E 2 Volcano plot of aberrantly expressed lncRNAs in glioma. Red circles indicate higher lncRNA expression (#|log2FC#|>2 and P-adj < 0.01). Black circles indicate lncRNAs without significant differential expression. The X-axis represents log2FoldChange and the Y-axis -log10 (adjusted FDR). Volcano plot produced by ggplot2 R package. lncRNA, long noncoding RNAs SONG ET AL. | 19519
The effect of axial shallow groove on the nonlinear dynamic response and buckling of laminated cylindrical shells subjected to radial compression loading was investigated. Based on the first-order shear deformation theory (FSDT), the nonlinear dynamic equations involving the transverse shear deformation and initial geometric imperfections were derived with the Hamilton philosophy. The axial shallow groove of the laminated composite cylindrical shell was treated as the initial geometric imperfections in the dynamic equations. A semi-analytical method of expanding displacements and loads along the circumferential direction and employing the finite difference method along the axial direction and in the time domain is used to solve the governing equations and obtain the dynamic response of the laminated shell. The B-R criterion was employed to determine the critical loads of dynamic buckling of the shell. The effects of the parameters of the shallow groove on the dynamic response and buckling were discussed in this paper and the results show that the axial shallow grooves greatly affect the dynamic response and buckling.
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