BackgroundMicroRNAs have been considered as a kind of potential novel biomarker for cancer detection due to their remarkable stability in the blood and the characteristics of their expression profile in many diseases.MethodsWe performed microarray-based serum miRNA profiling on the serum of twenty nasopharyngeal carcinoma patients at diagnosis along with 20 non-cancerous individuals as controls. This was followed by a real-time quantitative Polymerase Chain Reaction (RT-qPCR) in a separate cohort of thirty patients with nasopharyngeal carcinoma and thirty age- matched non-cancerous volunteers. A model for diagnosis was established by a conversion of mathematical calculation formula which has been validated by analyzing 74 cases of patients with nasopharyngeal carcinoma and 57 cases of non-cancerous volunteers.ResultsThe profiles showed that 39 and 17 miRNAs are exclusively expressed in the serum of non-cancerous volunteers and of patients with nasopharyngeal carcinoma respectively. 4 miRNAs including miR-17, miR-20a, miR-29c, and miR-223 were found to be expressed differentially in the serum of NPC compared with that of non-cancerous control. Based on this, a diagnosis equation with Ct difference method has been established to distinguish NPC cases and non-cancerous controls and validated with high sensitivity and specificity.ConclusionsWe demonstrate that the serum miRNA-based biomarker model become a novel tool for NPC detection. The circulating 4-miRNA-based method may provide a novel strategy for NPC diagnosis.

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA (mRNA) and protein synthesis. Recent studies have shown that some miRNAs are involved in the progression of nasopharyngeal carcinoma (NPC). However, the aberrant miRNAs implicated in different clinical stages of NPC remain unknown and their functions have not been systematically studied.MethodsIn this study, miRNA microarray assay was performed on biopsies from different clinical stages of NPC. TargetScan was used to predict the target genes of the miRNAs. The target gene list was narrowed down by searching the data from the UniGene database to identify the nasopharyngeal-specific genes. The data reduction strategy was used to overlay with nasopharyngeal-specifically expressed miRNA target genes and complementary DNA (cDNA) expression data. The selected target genes were analyzed in the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The microRNA-Gene-Network was build based on the interactions of miRNAs and target genes. miRNA promoters were analyzed for the transcription factor (TF) binding sites. UCSC Genome database was used to construct the TF-miRNAs interaction networks.ResultsForty-eight miRNAs with significant change were obtained by Multi-Class Dif. The most enriched GO terms in the predicted target genes of miRNA were cell proliferation, cell migration and cell matrix adhesion. KEGG analysis showed that target genes were significantly involved in adherens junction, cell adhesion molecules, p53 signalling pathway et al. Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-29a/c, miR-34b, miR-34c-3p, miR-34c-5p, miR-429, miR-203, miR-222, miR-1/206, miR-141, miR-18a/b, miR-544, miR-205 and miR-149 may play important roles on the development of NPC. We proposed an integrative strategy for identifying the miRNA-mRNA regulatory modules and TF-miRNA regulatory networks. TF including ETS2, MYB, Sp1, KLF6, NFE2, PCBP1 and TMEM54 exert regulatory functions on the miRNA expression.ConclusionsThis study provides perspective on the microRNA expression during the development of NPC. It revealed the global trends in miRNA interactome in NPC. It concluded that miRNAs might play important regulatory roles through the target genes and transcription factors in the stepwise development of NPC.

Dysregulation of microRNA (miRNA) biogenesis is implicated in cancer development and progression. Dicer and Drosha are established regulators of miRNA biogenesis. In this study, we used a miRNA array to evaluate the miRNA expression profiles in nasopharyngeal carcinoma (NPC) samples. The significance analysis of microarrays showed a global downregulation of miRNA expression in NPC samples compared with normal nasopharyngeal epithelial tissues. Notably, miR-18a, a member of the oncogenic miR-17-92 cluster, was upregulated in the NPC samples and cell lines. Clinical parameter studies showed that higher levels of miR-18a correlated with NPC advanced stage, lymph node metastasis, Epstein-Barr virus infection and a higher death rate from NPC, indicating oncogenic roles in NPC development. The expression levels of miR-18a and Dicer1 were inversely related in NPC tissues. Further studies demonstrated that miR-18a negatively regulated Dicer1 by binding to the 3' untranslated regions of Dicer1. In vitro and in vivo biological function assays showed that miR-18a promoted the growth, migration and invasion of NPC cells by regulating Dicer1 expression, which caused the global downregulation of miRNA expression levels including miR-200 family and miR-143. Furthermore, we found that the epithelial mesenchymal transition marker E-cadherin and the oncogene K-Ras were aberrantly expressed after miR-18a transduction, and these alterations were directly induced by downregulation of the miR-200 family and miR-143. Collectively, our findings indicate that miR-18a plays an oncogenic role in the development of NPC by widespread downregulation of the miRNome and could be a potential therapeutic target for NPC.

A previous study demonstrated that miR-126 expression was significantly downregulated in highly metastatic colon cancer cells. This study was to investigate the biological function of miR-126 and its regulation of target genes in colon cancer cells. Quantitative PCR was used to detect miR-126 expression in colon cancer SW480 and SW620 cells. MTT assay was to measure the changed cell viability after miR-126 mimics transfection. Wound healing and Transwell migration and invasion assays measured capacity of tumor cell migration and invasion of SW480 and SW620 cells after miR-126 transfection. Luciferase reporter assay and Western blot were used to assess both transcriptional and expression levels of one of the miR-126 target genes (i.e., CXCR4). Levels of miR-126 expression were lower in colon cancer SW480 and SW620 cells than in the adjacent normal epithelial tissues (P < 0.05). Transfection of miR-126 mimics significantly reduced colon cancer cell viability compared to NC cells (P < 0.05). The wound healing and Transwell migration and invasion assays showed that miR-126 mimics inhibited SW480 and SW620 cell migration and invasion capacity. Bioinformatics predicted that CXCR4 is one of the miR-126 target genes. Indeed, luciferase reporter assay and Western blot confirmed that CXCR4 is a miR-126 target gene. Expression of miR-126 inhibited colon cancer cell viability and reduced tumor cell migration and invasion capacity by its negative regulation of CXCR4 expression.

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We observed that Drosha and Dicer expression was dysregulation in NPC compared with healthy control samples and was significantly correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise that the expression levels of Dicer and Drosha could be used as potential prognostic biomarkers for NPC.

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and frequently evolving drug resistance. Although there is growing consensus that noncoding ribonucleic acids (ncRNAs) are modulators of TLE, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of ncRNAs in TLE remains limited. In the current study, we constructed DNA methylation profiles from 30 TLE patients and 30 healthy controls for ncRNAs, primarily focusing on long ncRNAs (lncRNAs) and microRNAs (miRNAs), by reannotating data of DNA methylation BeadChip. Statistics analyses have revealed a global hypermethylation pattern in miRNA and lncRNA gene in TLE patients. Bioinformatic analyses have found aberrantly methylated miRNAs and lncRNAs are related to ion channel activity, drug metabolism, mitogen-activated protein kinase (MAPK) signaling pathway, and neurotrophin signaling pathway. Aberrantly methylated ncRNA and pathway target might be involved in TLE development and progression. The methylated and demethylated ncRNAs identified in this study provide novel insights for developing TLE biomarkers and potential therapeutic targets.