Project description:Purpose: Nasopharyngeal carcinoma (NPC) is a common malignant carcinoma of the head and neck, and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.Thus, more studies are needed to identify novel critical molecular events and key hub genes to develop novel diagnostic and therapeutic strategies for the management and treatment of NPC. Methods: In the present study, we systematically analyzed four independent NPC transcriptomic da-tasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC. We found totally 170 common overlapping differentially expressed genes (DEGs) in the four NPC datasets. GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC. Protein-protein interaction (PPI) network analysis identified a 15 hub-gene core network with overexpressed kinesin family member 2C (KIF2C) as a central regulator. Results: Loss-of-function study demonstrated that knockdown of KIF2C significantly inhibited cell growth and cell motility, and delayed cell cycle progression, accompanied with dramatic mitotic defects in spindle formation in NPC cells. RNA-seq analysis revealed that KIF2C knockdown led to deregulation of various downstream genes. KIF2C could also regulate the AKT/mTOR pathways, and enhance paclitaxel sensitivity in NPC cells. Conclusions: Taken together, our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.
Project description:MicroRNAs are biomarkers of prognosis and survival for many types of cancer. We evaluated whether microRNAs can predict the survival and efficacy of concurrent chemotherapy in nasopharyngeal carcinoma (NPC) patients. We retrospectively analyzed microRNA expression in 312 paraffin-embedded NPC specimens and 18 normal nasopharyngeal tissues using microarray. We found Forty-one microRNAs are differentially expressed between NPC and normal tissues, and a five-microRNA signature can predict survival independent of stage. NPC patients with the low-risk microRNA signature have a favorable response to concurrent chemotherapy. microRNA profiling of nasopharyngeal carcinoma tissues vs. normal nasopharyngeal tissues 312 paraffin-embedded nasopharyngeal carcinoma tissues and 18 paraffin-embedded normal nasopharyngeal tissues
Project description:1. To determine the association between LVD and clinico-pathologic variables in archived colorectal cancer and Nasopharyngeal carcinoma specimens
2. To determine the association between VEGF-C,-D expression with COX-2 expression and clinico-pathologic variables in colorectal cancer and Nasopharyngeal carcinoma
3. To determine the effect of celecoxib on lymphangiogenesis in Nasopharyngeal carcinoma Lymphangiogenesis and factors modulating lymphangiogenesis are associated with clinico-pathological outcome in Nasopharyngeal carcinoma and colorectal cancer. Celecoxib down-regulates lymphangiogenesis Archival colorectal cancer and Nasopharyngeal carcinoma tumor specimens will be obtained from the Department of Pathology. To determine the effect of celecoxib on lymphangiogenesis in Nasopharyngeal carcinoma, the investigators intend to analyze archived specimens collected in a previously conducted study. Colorectal tumor and nodal specimens and Nasopharyngeal carcinoma primary will be examined for MVD, LVD and growth factor expression using established haematoxylin and eosin and immunohistochemical techniques. Quantification of LVD and MVD shall be performed by two pathologists blinded to clinico-pathological variables using standardised methods.
Project description:microRNA profiles of exosomes :Exosomes from two nasopharyngeal carcinoma cell line TW03M-oM-<M-^HEBV+M-oM-<M-^Iand TW03M-oM-<M-^HEBV-M-oM-<M-^I and Exosomes from nasopharyngeal epithelial cells NP69 Two-condition experiment, Exosomes from two nasopharyngeal carcinoma cell line vs.one normal epithelium cell line. Biological replicates:1 Exosomes from nasopharyngeal carcinoma cell line TW03M-oM-<M-^HEBV+M-oM-<M-^I, 1 Exosomes from nasopharyngeal carcinoma cell line TW03M-oM-<M-^HEBV-M-oM-<M-^I,1 Exosomes from nasopharyngeal epithelial cells NP69.
Project description:Nasopharyngeal carcinoma (NPC) remains a majoy health problem worldwide, specially in Southeast China. In order to find the new candidate genes and molecular markers that are associated with nasopharyngeal carcinoma (NPC), this study focused on the screening NPC relative genes by gene expression profile. Keywords: disease state analysis 23 NPC biopsies and 15 nasopharynx chronic phlogistic biopsies were used to screen NPC relative genes by BioStarH-141s (2004) profile gene chips which contained 14112 points of full length human genes. The tumor samples were labeled with Cy5-dUTP.The nasopharyngeal phlogistic tissues were labeled with Cy3-dUTP. Biostatistics and bioinformatics were also used to analyse the differently expressed genes.
Project description:Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering the clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to cyclin-dependent kinases (CDKs) inhibitors, especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced anti-neoplastic activities both in vitro and in vivo. An integrative analysis using both whole-transcriptome sequencing (RNA-Seq) and chromatin-immunoprecipitation sequencing (ChIP-Seq) pinpointed oncogenic transcriptional amplification mediated by Super-Enhancer (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated network identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2 and a long non-coding RNA, TP53TG1. These transcripts were highly and specifically expressed in NPC, and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK and TEAD1) may help establish and maintain SE activity across the genome. Our data together established the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimen for this disease.
Project description:Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering the clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to cyclin-dependent kinases (CDKs) inhibitors, especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced anti-neoplastic activities both in vitro and in vivo. An integrative analysis using both whole-transcriptome sequencing (RNA-Seq) and chromatin-immunoprecipitation sequencing (ChIP-Seq) pinpointed oncogenic transcriptional amplification mediated by Super-Enhancer (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated network identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2 and a long non-coding RNA, TP53TG1. These transcripts were highly and specifically expressed in NPC, and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK and TEAD1) may help establish and maintain SE activity across the genome. Our data together established the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimen for this disease.
Project description:Recent studies have revealed that long non-coding RNAs (lncRNAs) participate in all steps of cancer initiation and progression by regulating protein coding genes at the epigenetic, transcriptional and post-transcriptional levels. LncRNAs are in turn regulated by other genes, forming a complex regulatory network. The regulation networks between the p53 tumor suppressor and lncRNAs in nasopharyngeal carcinoma (NPC) remain unclear. The aim of this study was to investigate the regulatory roles of the TP53 gene in regulating lncRNA and mRNA expression profiles in NPC cell line HNE2. p53 induced gene expression in human nasopharyngeal carcinoma cell line HNE2 was measured at 0, 12, 24 and 48 hours after transfected by pCMV-p53 plasmid.