Differential expressed miRNAs in Multi-stages and Lymphoid node metastasis of Nasopharyngeal Carcinoma
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ABSTRACT: According to the evolution of the NPC, with normal time series, we identified microRNAs (miRNAs) showing robust differential expression between nasopharyngeal carcinomas (NPCs) and normal healthy nasopharyngeal epithelial samples. This research use miRNA chip testing at different stages in 12 cases of NPC (TNM Ⅰ - II, III, IV each stage 4 cases), 4 patients matched sample and transfer lymphoma 6 samples. Analysis the difference miRNA distribution of in the NPC development, adopt modern bioinformatics methods selection differentially expressed genes. we study the miRNA dynamic expression profiles in different clinical stages of nasopharyngeal carcinoma and NPC lymphoid node metastasis. Samples were taken from a range of tumors of different stages. 6 cases of normal, 4 respective cases of stage I or II, III, IV and lymph node metastasis. The microdissection was performed with Methyl Green staining to separate tumor cells to non-tumor cells.
Project description:According to the evolution of the NPC, with normal time series, we identified microRNAs (miRNAs) showing robust differential expression between nasopharyngeal carcinomas (NPCs) and normal healthy nasopharyngeal epithelial samples. This research use miRNA chip testing at different stages in 12 cases of NPC (TNM Ⅰ - II, III, IV each stage 4 cases), 4 patients matched sample and transfer lymphoma 6 samples. Analysis the difference miRNA distribution of in the NPC development, adopt modern bioinformatics methods selection differentially expressed genes.
Project description:Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. We determined the genomic landscape of 52 NPC cases with SNP-array analysis. This approach identified multiple recurrent SCNVs, with the most frequent deletion peak spanning the CDKN2A gene on 9p21. Additional SCNVs involving established cancer genes including CCND1, AKT2, MYC and TP53 were observed. Notably, we identified that one component of the SWI/SNF complex, ARID1A, was frequently deleted in NPC. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen nasopharyngeal carcinoma biopsy tissues Copy number analysis of Affymetrix 250K SNP arrays was performed for 52 nasopharyngeal carcinoma samples. Please note that the sample characteristics 'primary tumor size, metastasis, and regional lymph node' represents T, M and N in WHO TNM staging of nasopharyngeal cancer (according to American Joint Committee on Cancer (AJCC)), respectively.
Project description:Analysis of differential expression between NPC and non-NPC tissues at miRNA expression level. We used a miRNA microarray platform to investigate the profile between NPC tissues and normal nasopharyngeal tissues to evaluate the relationship between miRNA expression and NPC. Recognition of the aberrant miRNAs and enrichment pathway analysis of predicted target gene may provide some clues to estimate the mechanism of miRNA effects on NPC carcinogenesis mediated by miRNA-mRNA regulation. Total RNA was extracted from 8 NPC tissues compared to 4 nasopharyngeal tissues. We peformed the Illumina miRNA microarray to identify the differentially expressed miRNA between NPC tissues and normal nasopharyngeal tissues.
Project description:Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with striking racial and geographic distribution differences. Furthermore, numerous genetic linkage and association studies have reported a few genes contributing to the risk of this malignancy. The identification of susceptibility genes contributing to NPC would assist in predicting individual and population risk of NPC development and would help to clarify the pathogenesis relevant to this disorder. Argonaute 2 (AGO2), a central component of RNA-induced silencing complex, plays critical roles in cancer. We examined whether the single nucleotide polymorphisms (SNPs) of AGO2 were related to the risk of nasopharyngeal carcinoma (NPC). Twenty-five tag SNPs within AGO2 were genotyped in Guangxi population consisting of 855 NPC patients and 1036 controls. The SNPs significantly associated with NPC were further replicated in Guangdong population consisting of 996 NPC patients and 972 controls. Functional experiments were conducted to examine the biologic roles of AGO2 in NPC. A significantly increased risk of advanced lymph node metastasis of NPC was identified for the AGO2 rs3928672 GA + AA genotype compared with GG genotype in both the Guangxi and Guangdong populations. In addition, AGO2 knockdown reduced cell proliferation, induced apoptosis, and inhibited migration of NPC cells. Furthermore, gene expression microarray showed that genes altered following AGO2 knockdown were clustered in tumorigenesis and metastasis relevant pathways. Our findings suggest that the genetic polymorphism in AGO2 may be a risk factor for the advanced lymph node metastasis of NPC in Chinese populations, and AGO2 acts as an oncogene in the development of NPC.
Project description:Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers, NPC metastasis has become the main cause of treatment failure. The molecular basis regulating NPC metastasis remains obscure. Here we discovered a gene named LACTB Highly expressed in NPC tissues and aimed to investigate its role and regulatory mechanism in the metastasis of NPC.LACTB was found to promote NPC cellular motility in vitro and metastasis in vivo via the activation of the ERBB3/EGFR-ERK pathway on a histone H3 depending manner. Also, the elevated expression of LACTB in the primary NPC correlated with patient poor survival, indicating LACTB as a potential prognostic predictor and an anti-metastasis therapeutic target.
Project description:Most of the NPC patients suffer from local recurrences and distant metastases within 1.5 years after radiotherapy due to radioresistance. Distinct patterns of miRNa expression and signatures were found in NPC, and have been used to associate them with cell proliferation, apoptosis, invasion and metastasis, but few miRNA expression profiling studies have been focused on the tumor radioresistance.We used miRNA expression microarray analyses to identify the difference of miRNA in radioresistant NPC CNE2-IR cells and radiosensitive CNE2 cells. Radioresistant subclone of nasopharyngeal carcinoma CNE2-IR cell line was cultured and produced according to the experienment schedule to undergo five rounds of sublethal dose of irradiation (11 Gy),and the parent cell line CNE2 sensitive to radiotherapy as the control
Project description:Increasing evidence has demonstrated a significant role for long non-coding RNAs (lncRNAs) in tumorigenesis. However, their functions in nasopharyngeal carcinoma (NPC) metastasis remain largely unknown. In this study, a model compared high and low metastatic NPC cell lines (5-8F vs. 6-10B and S18 vs. S26)was constructed to determine the expression profile of lncRNAs using the microarray analysis, and we found 167 lncRNAs and 209 mRNAs were differentially expressed. Validationof 26 significantly dysregulated lncRNAs by qRT-PCR showed the expression patterns of 22 lncRNAs were in accordance with the microarray data. Furthermore, the expression level of ENST00000470135, which was the most upregulated lncRNA in high metastatic cell lines, was significantly higher in NPC cell lines and tissues with lymph node metastasis(LNM)and knocking down ENST00000470135 suppressed the migration, invasion and proliferation of NPC cells in vitro. In conclusion, our study revealed expression patterns of lncRNAs in NPC metastasis. The dysregulated lncRNAs may act as novel biomarkers and therapeutic targets for NPC.
Project description:The expression of miRNA in cancer tissues of gastric cancer patients with different lymph node stages was compared. N0 indicated no lymph node metastasis, and N3 indicated 7 or more lymph node metastasis
Project description:Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and South East Asia where more than 50,000 new cases are diagnosed each year. We used microarrays to identify down or upregulated genes in NPC compared with non-malignant controls. Experiment Overall Design: Snap frozen nasopharyngeal biopsies from 25 patients with histologically confirmed undifferentiated NPC were included in the microarray analysis. Controls were obtained from 3 patients with no evidence of malignancy.
Project description:Nasopharyngeal carcinoma (NPC) is rare malignancy in most parts around the world but common in Southern China and Southeast Asia, Annually, approximately 80,000 new NPC cases and 50,000 deaths are reported worldwide. In NPC, recent advances have shown that many genes that are predominantly or even exclusively silenced by DNA methylation in epithelial cells during pathogenesis of NPC. However, the causal relationship between DNA methylation status and outcome in NPC remains not well understood. To investigate this problem, we used Illumina 450K BeadChips to examined methylation patterns and survival in NPC. and ultimately provided insight into prognostic value of DNA methylation in NPC clinical management. We employed Illumina Human Methylation450K Beadchip to analyze a genome-wide of DNA methylation in a cohort of 48 samples (between 24 nasopharyngeal carcinoma tissues and 24 normal nasopharyngeal epithelial tissues) to identify aberrant methylation genes.