Search

The purpose of the present study was to screen the key genes associated with laryngeal carcinoma and to investigate the molecular mechanism of laryngeal carcinoma progression. The gene expression profile of GSE10935 [Gene Expression Omnibus (GEO) accession number], including 12 specimens from laryngeal papillomas and 12 specimens from normal laryngeal epithelia controls, was downloaded from the GEO database. Differentially expressed genes (DEGs) were screened in laryngeal papillomas compared with normal controls using Limma package in R language, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape software and modules were analyzed using MCODE plugin from the PPI network. Furthermore, significant biological pathway regions (sub-pathway) were identified by using iSubpathwayMiner analysis. A total of 67 DEGs were identified, including 27 up-regulated genes and 40 down-regulated genes and they were involved in different GO terms and pathways. PPI network analysis revealed that Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) was a hub protein. The sub-pathway analysis identified 9 significantly enriched sub-pathways, including glycolysis/gluconeogenesis and nitrogen metabolism. Genes such as phosphoglycerate kinase 1 (PGK1), carbonic anhydrase II (CA2), and carbonic anhydrase XII (CA12) whose node degrees were >10 were identified in the disease risk sub-pathway. Genes in the sub-pathway, such as RASSF1, PGK1, CA2 and CA12 were presumed to serve critical roles in laryngeal carcinoma. The present study identified DEGs and their sub-pathways in the disease, which may serve as potential targets for treatment of laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that progesterone has neuroprotective effects in the central nervous system (CNS) following traumatic brain injury (TBI). Numerous cellular mechanisms have been reported to be important in the neuroprotective effects of progesterone, including the reduction of edema, inflammation and apoptosis, and the inhibition of oxidative stress. However, the effect of progesterone on neuronal protection following TBI remains unclear. The present study aimed to investigate the effects of progesterone on the expression of Nogo-A, an inhibitor of axonal growth, glial fibrillary acidic protein (GFAP), a main component of the glial scar and growth-associated protein-43 (GAP-43), a signaling molecule in neuronal growth in TBI rats. The TBI model was produced by the weight drop method. In total, 75 rats were assigned to three groups: the sham group, TBI group with vehicle treatment and TBI group with progesterone treatment. The protein expression of Nogo-A, GFAP and GAP-43 in the cortex and the hippocampus was examined by immuno-cytochemistry. TBI rats significantly increased the expression of Nogo-A, GFAP, and GAP-43 at 1, 3, 7 and 14 days post-injury Progesterone significantly decreased the expression of Nogo-A and GFAP, and upregulated the GAP-43 protein. Our findings suggested that progesterone promotes neuroprotection following TBI by inhibiting the expression of Nogo-A and GFAP, and increasing GAP-43 expression. [ABSTRACT FROM AUTHOR]

Podocalyxin (PODXL) has been found to increase the aggressive phenotype of a number of cancers, including astrocytoma. In addition, the progression of astrocytoma has been associated with sperm-associated antigen 9 (SPAG9), a recently characterized oncoprotein. In the present study, the association between SPAG9 and PODXL in human astrocytoma invasion and the underlying mechanisms were investigated for the first time, to the best of our knowledge. Overexpression and knockdown of SPAG9 were performed in SW1783 (grade III astrocytoma) and U87 (grade IV astrocytoma; glioblastoma) cells, respectively. PODXL expression at both the mRNA and the protein level, as well as the PODXL gene promoter activity, were significantly increased and decreased in parallel with the overexpression and knockdown of SPAG9 in astrocytoma cells; these effects were blocked by the selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 (5 μM) and restored by the JNK agonist anisomycin (25 ng/ml), respectively. SPAG9 overexpression significantly increased cell invasion and matrix metalloproteinase-9 (MMP-9) expression in SW1783 cells, and this effect was reversed by knockdown of PODXL. In U87 cells, knockdown of SPAG9 markedly d ecreased cell invasion and MMP-9 expression, which was completely restored by overexpression of PODXL. In conclusion, it was demonstrated in the present study that SPAG9 upregulates PODXL expression in human astrocytoma cells at the PODXL gene promoter/transcriptional level through a JNK-dependent mechanism and that PODXL is a critical mediator of the promoting effect of SPAG9 on astrocytoma cell invasion, possibly through upregulation of MMP-9 expression. This study provides novel insights into the molecular mechanisms involved in astrocytoma invasion. [ABSTRACT FROM AUTHOR]