Using microarray data, the present study identified differentially expressed microRNAs (miRNAs)

Using microarray data, the present study identified differentially expressed microRNAs (miRNAs) and evaluated their regulatory characteristics in high-grade glioma patients, with the aim to further the understanding into the underlying etiology of the condition. the tumorigenesis of other types of cancer. Moreover, the expression levels of hsa-miR-1908, hsa-miR-4656 and hsa-miR-4680 have been identified to significantly correlate with the survival rate. Enrichment analysis of the dysregulated target genes revealed that the selected miRNAs primarily affect biological processes in the nervous system and the protein phosphorylation process. Therefore, the results may offer a new understanding into the pathogenesis of high-grade glioma. was detected to have the highest degree. Figure 2 Regulatory network constructed with dysregulated miRNAs and target genes. Interactions between target genes are shown with a buy Z-360 dotted line. Items in red represent overexpressed molecules in grade IV patients, while those in blue represent downregulated … Enrichment analysis Enrichment analysis of the differentially expressed target genes identified two KEGG pathways and four GO items over-represented with dysregulated target genes (Table II). The two KEGG pathways were retrograde endocannabinoid signaling and dopaminergic synapse, which are both involved in the nervous system. In addition, one of the GO items, the postsynaptic membrane (GO:0045211), is also associated with the nervous system. The remaining three GO items were shown to Itga7 be associated with the protein phosphorylation process, including protein serine/threonine phosphatase activity (GO:0004722), JUN phosphorylation (GO:0007258) buy Z-360 and protein dephosphorylation (GO:0006470). Table II Pathways and GO items enriched with differentially expressed genes. Discussion To identify differentially expressed miRNAs and determine their regulatory characteristics in high-grade glioma patients, PLS analysis was performed. In total, six miRNAs were identified to be dysregulated. Among them, hsa-miR-21 has been previously reported to exhibit a significant correlation with tumor grade and prognosis (21,22). In addition, the expression of hsa-miR-612 has been reported to be associated with magnetic resonance imaging features of glioblastoma multiforme (23). The results of the present study further confirmed the involvement of the two miRNAs in the progression of glioma. In addition, one of the target genes of miR-612 is PTEN. PTEN is a tumor suppressor that negatively regulates the protein kinase B/Akt-dependent cell survival pathway (24). Therefore, depression of PTEN may buy Z-360 impact its negative regulation of tumor cell survival and contribute to the deterioration of the disease. None of the remaining four miRNAs have been previously reported to be associated with glioma. However, hsa-miR-1908 has been reported to be associated with the metastasis or tumorigenesis of other types of tumor, including chordomas (25), hepatoma (26) and melanoma (27). In addition, hsa-miR-4680, hsa-miR-4656 and hsa-miR-4467 have been hypothesized to be associated with breast tumor (28). For miR-4680, one of its target genes is definitely FN1, which is a hub gene that was found out to have the highest degree among the prospective genes. The protein encoded by this gene is definitely fibronectin, which is definitely involved in cell adhesion and migration processes. A previous study reported a significant correlation between this gene and malignant glioma (29), indicating the potential regulatory mechanism of miR-4680 in the development of glioma. Survival analysis also exposed the manifestation levels of hsa-miR-1908, hsa-miR-4656 and hsa-miR-4680 were significantly associated with the survival rate of the individuals (Fig. 1). Moreover, the constructed network of dysregulated miRNAs and target genes exposed that hsa-miR-21, hsa-miR-612 and hsa-miR-4656 share a number of target genes, indicating that they may impact related biological processes. Thus, further investigation of these miRNAs is definitely warranted. Pathway enrichment analysis of the dysregulated buy Z-360 target genes revealed the differentially indicated miRNAs primarily impact pathways in the nervous system, including retrograde endocannabinoid signaling and the dopaminergic synapse. GO analysis additionally exposed the over-representation of dysregulated target genes in the protein phosphorylation process. The GO:0004722 item of protein serine/threonine phosphatase activity exhibited the most significant enrichment. A earlier study reported the alteration of striatal dopaminergic function in glioma development (30). Furthermore, dysregulation of serine/threonine phosphatase calcineurin.