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 comparing 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. Bioinformatic analysis indicated that the dysregulated mRNAs participated in important biological regulatory functions in NPC. Validation of 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:Recent studies have revealed that long non-coding RNAs participate in all steps of cancer initiation and progression by regulating protein-coding genes at the epigenetic, transcriptional, and post-transcriptional levels. Long non-coding RNAs are in turn regulated by other genes, forming a complex regulatory network. The regulation networks between the p53 tumor suppressor and these RNAs in nasopharyngeal carcinoma remains unclear. The aims of this study were to investigate the regulatory roles of the TP53 gene in regulating long non-coding RNA expression profiles and to study the function of a TP53-regulated long non-coding RNA (LOC401317) in the nasopharyngeal carcinoma cell line HNE2. Long non-coding RNA expression profiling indicated that 133 long non-coding RNAs were upregulated in the human NPC cell line HNE2 cells following TP53 overexpression, while 1057 were downregulated. Among these aberrantly expressed long non-coding RNAs, LOC401317 was the most significantly upregulated one. Further studies indicated that LOC401317 is directly regulated by p53 and that ectopic expression of LOC401317 inhibits HNE2 cell proliferation in vitro and in vivo by inducing cell cycle arrest and apoptosis. LOC401317 inhibited cell cycle progression by increasing p21 expression and decreasing cyclin D1 and cyclin E1 expression and promoted apoptosis through the induction of poly(ADP-ribose) polymerase and caspase-3 cleavage. Collectively, these results suggest that LOC401317 is directly regulated by p53 and exerts antitumor effects in HNE2 nasopharyngeal carcinoma cells.
Project description:Recent studies demonstrated that long non-coding RNAs (lncRNAs) deregulated in many cancer tissues including nasopharyngeal carcinoma (NPC) and had critical roles in cancer progression and metastasis. In this study, we aimed to assess a lncRNA LINC01420 expression in NPC and explore its role in NPC pathogenesis. Our research revealed that the expression level of LINC01420 in NPC tissues were higher than nasopharyngeal epithelial (NPE) tissues. Moreover, NPC patients with high LINC01420 expression level showed poor overall survival. Knockdown LINC01420 inhibited NPC cell migration and invasion in vitro. In summary, LINC01420 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients.
Project description:Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16) mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN) tissues from three patients with high-throughput RNA sequencing (RNA-seq). In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE) in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO) terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA) network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer.
Project description:Non-coding RNAs (ncRNAs) regulate numerous genes and influence the progression of various human diseases, including cancer. The role of regulatory ncRNAs implicated in nasopharyngeal carcinoma (NPC), as well as their target genes, remains unclear. The present study aimed to investigate specific long non-coding (lnc)RNAs, circular RNAs (circRNAs) and mRNAs associated with the molecular pathogenesis of NPC, and to predict the underlying target genes of specific lncRNAs and circRNAs. The expression levels of lncRNAs, circRNAs and mRNAs in NPC and chronic nasopharyngitis tissues were detected and analyzed using microarray and bioinformatics techniques. A total of 2.80% lncRNAs (425 upregulated and 431 downregulated) were significantly differentially expressed (DE) between the two tissue types. Additionally, 0.96% circRNAs (18 upregulated and 13 downregulated) were significantly DE, while 2.94% mRNAs (426 upregulated and 341 downregulated) were significantly DE between the two tissue types. In total, 420 NPC-associated nearby encoding genes (196 up- and 224 downregulated) of the DE lncRNAs were identified. Overlap analysis identified 23 DE circRNAs and their corresponding target genes, with 37 microRNAs and 50 mRNAs, from which 14 interaction networks were constructed. Subsequent pathway analysis revealed 221 DE target genes corresponding to 31 key signaling pathways associated with NPC, 14 of which may represent hub genes associated with NPC pathophysiology. Thus, certain lncRNAs, circRNAs and mRNAs are aberrantly expressed in NPC tissues, and partially specific lncRNAs, circRNAs and their target genes may influence the tumorigenesis and progression of NPC. Target prediction and regulatory network identification may help to determine the pathogenic mechanisms of NPC.
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. Overall design: Total RNA recovered from two sets of cell lines (5-8F vs. 6-10B and S18 vs. S26) were used to acquire different expression profiles of mRNAs and lncRNAs in high metastatic potential and low metastatic potential nasopharyngeal carcinoma cell lines.
Project description:Long non-coding RNAs (lncRNAs) were found to play roles in various cancers, including nasopharyngeal carcinoma. In this study, we focused on the biological function of the lncRNA FAM133B-2 in the radio-resistance of nasopharyngeal carcinoma. The RNA-seq and qRT-PCR analysis showed that FAM133B-2 is highly expressed in the radio-resistant nasopharyngeal carcinoma cells. The following biochemical assays showed that FAM133B-2 represses the nasopharyngeal carcinoma radio-resistance and also affects the apoptosis and proliferation of nasopharyngeal carcinoma cells. Further investigations suggested that miR-34a-5p targets FAM133B-2 and also regulates the cyclin-dependent kinase 6 (CDK6). All these results suggested that the lncRNA FAM133B-2 might function as a competitive endogenous RNA (ceRNA) for miR-34a-5p in nasopharyngeal carcinoma radio-resistance, thus it may be regarded as a novel prognostic biomarker and therapeutic target in nasopharyngeal carcinoma diagnosis and treatment.