scholarly journals Integrated analysis of the miRNA-mRNA network associated with LMP1 gene in nasopharyngeal carcinoma

2019 ◽  
Author(s):  
Yang Yang ◽  
Wen Liu ◽  
Yan Zhang ◽  
Shuo Wu ◽  
Bing Luo

AbstractEpstein-Barr virus oncogenic latent membrane protein 1 (LMP1) has been known to play important roles in nasopharyngeal carcinoma (NPC). LMP1 gene also induced a variety of microRNAs (miRNAs) which bear pivotal roles in regulation of mRNAs expression. However, little was known about the global change of mRNAs and miRNAs induced by LMP1 gene in NPC. In our study, one NPC tissue microarray profile and two LMP1-associated microarray expression profiles data were downloaded from the Gene Expression Omnibus database. A protein-protein interaction network was constructed by using bioinformatics platform Gene-Cloud of Biotechnology Information (GCBI). 78 differentially expressed miRNAs and 3322 differentially expressed genes were identified in order to generate a macroscopic network between miRNAs and mRNAs associated with LMP1 gene. In addition, two significant models were generated to illustrate the expression tendency. Our study provided a way to reveal the interaction between miRNAs and mRNAs in LMP1 axis, bringing insights into the pathogenesis of NPC.

2020 ◽  
Vol 29 (4) ◽  
pp. 483-492
Author(s):  
Hanwei Wu ◽  
Yuchen Liu ◽  
Hongfang Duan ◽  
Xiaoqin Fan ◽  
Yujie Wang ◽  
...  

BACKGROUND: Circular RNAs (circRNAs) are endogenous RNAs that have a covalent closed cycle configuration. circRNAs have been found to be differentially expressed in many human cancers. Therefore, circRNAs may be ideal biomarkers for the diagnosis and treatment of cancer. However, we know very little about the function of circRNAs in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the circRNA expression profiles in NPC. METHODS: We utilized high-throughput RNA sequencing (RNA-Seq) to evaluate the circRNA expression profile in NPC A total of 13,561 unique circRNA candidates were detected. Selection of aberrantly expressed circRNAs was carried out using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. We carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to identify the biological functions of differentially expressed circRNAs. Moreover, bioinformatics analyses were implemented to predict the effects between circRNAs and cancer-related microRNAs (miRNAs), and we used Cytoscape to build a cancer-related circRNA-miRNA target gene map. Finally, to verify dysregulated circRNAs, quantitative real-time PCR was utilized. RESULTS: In NPC tissues, we found that 73 circRNAs were downregulated and 59 were upregulated. The top 12 candidate circRNAs were selected from several vital NPC pathways such as the human papillomavirus and Epstein-Barr virus infection signaling pathways (hsa05165 and hsa05169, respectively), Hepatitis B (hsa05161), and the Ras signaling pathway (hsa04014). A network map of circRNA-miRNA interactions of 12 differentially expressed circRNAs was built. Hsa_circ_0007637 expression distinguished NPC tissues from paired healthy tissues and NPC cell lines (HNE1 6-10B, 5-8F, CNE-2, and so on) from a normal epithelial (NP460) cell line. CONCLUSIONS: In this study, we investigated the profiles of differentially expressed circRNAs in NPC, and our results show that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development. This observation-based research identified dysregulated circRNAs in NPC, which may assist in the development of biomarkers for this disease. Further studies on the mechanisms and functions of these circRNAs may promote our understanding of NPC tumorigenesis.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yanhua Lei ◽  
Ping Guo ◽  
Xiuguo Li ◽  
Yuanyuan Zhang ◽  
Ting Du

Background.Vestibular schwannoma (VS) is benign, slow-growing brain tumor that negatively impacts patient quality of life, which may cause even death. This study aimed to explore key genes and microRNAs (miRNAs) associated with VS.Methods.The mRNA and miRNA expression profiles of VS downloaded from Gene Expression Omnibus (GEO) database were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified. Then, functional annotation and protein-protein interaction networks (PPI) of DEmRNAs were constructed. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed.Results.A total of 2627 DEmRNAs (1194 upregulated and 1433 downregulated DEmRNAs) and 21 DEmiRNAs (12 upregulated and 9 downregulated DEmiRNAs) were identified. ISG15, TLE1, and XPC were three hub proteins of VS-specific PPI network. A total of 2970 DEmiRNAs-DEmRNAs pairs were obtained. Among which, hsa-miR-181a-5p, hsa-miR-106-5p, and hsa-miR-34a-5p were the top three DEmiRNAs that covered most DEmRNAs. The functional annotation of DEmiRNA-target DEmRNAs revealed that the DEmiRNA-target DEmRNAs were significantly enriched in cGMP-PKG signaling pathway, adrenergic signaling in cardiomyocytes, and pathways in cancer.Conclusion.The results of this present study may provide a comprehensive understanding for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of VS and developing potential biomarkers of VS.


Epigenomics ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1795-1809 ◽  
Author(s):  
Haiyu Cao ◽  
Dong Li ◽  
Huixiu Lu ◽  
Jing Sun ◽  
Haibin Li

Aim: The aim of this study was to find potential differentially expressed long noncoding RNAs (lncRNAs) and mRNAs in systemic lupus erythematosus. Materials & methods: Differentially expressed lncRNAs and mRNAs were obtained in the Gene Expression Omnibus dataset. Functional annotation of differentially expressed mRNAs was performed, followed by protein–protein interaction network analysis. Then, the interaction network of lncRNA-nearby targeted mRNA was built. Results: Several interaction pairs of lncRNA-nearby targeted mRNA including NRIR-RSAD2, RP11-153M7.5-TLR2, RP4-758J18.2-CCNL2, RP11-69E11.4-PABPC4 and RP11-496I9.1-IRF7/ HRAS/ PHRF1 were identified. Measles and MAPK were significantly enriched signaling pathways of differentially expressed mRNAs. Conclusion: Our study identified several differentially expressed lncRNAs and mRNAs. And their interactions may play a crucial role in the process of systemic lupus erythematosus.


2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yiting Tian ◽  
Yang Xing ◽  
Zheng Zhang ◽  
Rui Peng ◽  
Luyu Zhang ◽  
...  

Gastric cancer (GC) is one of the most common malignancies in the world, with morbidity and mortality ranking second among all cancers. Accumulating evidences indicate that circular RNAs (circRNAs) are closely correlated with tumorigenesis. However, the mechanisms of circRNAs still remain unclear. This study is aimed at determining hub genes and circRNAs and analyzing their potential biological functions in GC. Expression profiles of mRNAs and circRNAs were downloaded from the Gene Expression Omnibus (GEO) data sets of GC and paracancer tissues. Differentially expressed genes (DEGs) and differentially expressed circRNAs (DE-circRNAs) were identified. The target miRNAs of DE-circRNAs and the bidirectional interaction between target miRNAs and DEGs were predicted. Functional analysis was performed, and the protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were established. A total of 456 DEGs and 2 DE-circRNAs were identified with 3 mRNA expression profiles and 2 circRNA expression profiles. GO analysis indicated that DEGs were mainly enriched in extracellular matrix and cell adhesion, and KEGG confirmed that DEGs were mainly associated with focal adhesion, the PI3K-Akt signaling pathway, extracellular matrix- (ECM)- receptor interaction, and gastric acid secretion. 15 hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, UBE2C, CCNB1, CD44, CXCL8, COL3A1, COL5A2, and THBS1) were identified from the PPI network. Furthermore, the survival analysis indicate that GC patients with a high expression of the following 9 hub DEGs, namely, BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C, had significantly worse overall survival. The circRNA-miRNA-mRNA network was constructed based on 1 circRNA, 15 miRNAs, and 45 DEGs. In addition, the 45 DEGs included 5 hub DEGs. These results suggested that hub DEGs and circRNAs could be implicated in the pathogenesis and development of GC. Our findings provide novel evidence on the circRNA-miRNA-mRNA network and lay the foundation for future research of circRNAs in GC.


2020 ◽  
Vol 19 ◽  
pp. 153303382095699
Author(s):  
Lei Liu ◽  
Hailing Wang ◽  
Chaohui Yan ◽  
Shudong Tao

Objective: We aim to identify several microRNAs (miRNAs/miRs)-messenger RNAs (mRNAs) biomarkers correlated to nasopharyngeal carcinoma (NPC) based on an integrated analysis of miRNA and mRNAs microarray expression profiles. Methods: The available mRNA and miRNA microarray datasets were retrieved from Gene Expression Omnibus (GEO) database according to pre-determined screening criteria. Differentially expressed miRNA and mRNAs (DEmiRNAs and DEmRNAs) were extracted between NPC and noncancerous nasopharyngeal tissues. The target genes of DEmiRNAs were predicted with miRTarBase followed by the construction of DEmiRNAs-target DEmRNAs network, and functional analyses were performed. The DEmiRNAs expressions were validated and the performance of these DEmiRNAs was assessed by the area under the curve (AUC) values. Finally, the correlations between DEmiRNAs and specific clinical factors were analyzed. Results: There were 1140 interaction pairs (including let-7d/f- MYC/ HMGA2 and miR-452- ITGA9) in DEmiRNAs-target DEmRNAs network. The GO annotation analysis showed that several genes such as MYC, HMGA2 and ITGA9 primarily participated in cellular process. KEGG analysis showed that these targets were associated with cell cycle and cancer-related pathways. Down-regulated let-7(-d and –f) and up-regulated miR-452 were verified in datasets. The AUC values of these 3 DEmiRNAs (let-7d, let-7-f and miR-452) was 0.803, 0.835 and 0.735, respectively. Besides, miR-452 was significantly related to survival rate of NPC patients. Conclusion: The findings implied let-7d/f- MYC/ HMGA2 and miR-452- ITGA9 might be promising targets for the detection and treatment of NPC.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Gao ◽  
Yu Zhao ◽  
Xuelei Ma ◽  
Ling Zhang

Abstract Background Competitive endogenous RNA (ceRNA) networks have revealed a new mechanism of interaction between RNAs, and play crucial roles in multiple biological processes and development of neoplasms. They might serve as diagnostic and prognosis markers as well as therapeutic targets. Methods In this work, we identified differentially expressed mRNAs (DEGs), lncRNAs (DELs) and miRNAs (DEMs) in sarcomas by comparing the gene expression profiles between sarcoma and normal muscle samples in Gene Expression Omnibus (GEO) datasets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were applied to investigate the primary functions of the overlapped DEGs. Then, lncRNA-miRNA and miRNA-mRNA interactions were predicted, and the ceRNA regulatory network was constructed using Cytoscape software. In addition, the protein–protein interaction (PPI) network and survival analysis were performed. Results A total of 1296 DEGs were identified in sarcoma samples by combining the GO and KEGG enrichment analyses, 338 DELs were discovered after the probes were reannotated, and 36 DEMs were ascertained through intersecting two different expression miRNAs sets. Further, through target gene prediction, a lncRNA–miRNA–mRNA ceRNA network that contained 113 mRNAs, 69 lncRNAs and 29 miRNAs was constructed. The PPI network identified the six most significant hub proteins. Survival analysis revealed that seven mRNAs, four miRNAs and one lncRNA were associated with overall survival of sarcoma patients. Conclusions Overall, we constructed a ceRNA network in sarcomas, which might provide insights for further research on the molecular mechanism and potential prognosis biomarkers.


Author(s):  
Xiandong Lin ◽  
Steven Wang ◽  
Keyu Lin ◽  
Jingfeng Zong ◽  
Qianlan Zheng ◽  
...  

Non-coding RNAs have been shown to play important regulatory roles, notably in cancer development. In this study, we investigated the role of microRNAs and circular RNAs in Nasopharyngeal Carcinoma (NPC) by constructing a circRNA-miRNA-mRNA co-expression network and performing differential expression analysis on mRNAs, miRNAs, and circRNAs. Specifically, the Epstein-Barr virus (EBV) infection has been found to be an important risk factor for NPC, and potential pathological differences may exist for EBV+ and EBV- subtypes of NPC. By comparing the expression profile of non-cancerous immortalized nasopharyngeal epithelial cell line and NPC cell lines, we identified differentially expressed coding and non-coding RNAs across three groups of comparison: cancer vs. non-cancer, EBV+ vs. EBV- NPC, and metastatic vs. non-metastatic NPC. We constructed a ceRNA network composed of mRNAs, miRNAs, and circRNAs, leveraging co-expression and miRNA target prediction tools. Within the network, we identified the regulatory ceRNAs of CDKN1B, ZNF302, ZNF268, and RPGR. These differentially expressed axis, along with other miRNA-circRNA pairs we identified through our analysis, helps elucidate the genetic and epigenetic changes central to NPC progression, and the differences between EBV+ and EBV- NPC.


Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 2937-2942 ◽  
Author(s):  
H Knecht ◽  
E Bachmann ◽  
P Brousset ◽  
K Sandvej ◽  
D Nadal ◽  
...  

This study of 52 European patients with Hodgkin's disease (HD) expressing the latent membrane protein 1 (LMP1) oncogene within diagnostic Hodgkin and Reed-Sternberg (HRS) cells was performed to detect LMP1 isolates carrying deletions and to characterize them at a molecular and histologic level. Deletions were identified in 5 cases, clustered near the 3′ end of the LMP1 gene, and histologically associated with numerous HRS cells. DNA sequencing showed homology with the deletions seen in the Asian nasopharyngeal carcinoma (NPC) isolates CAO and 1510. Our findings suggest that partial deletions of the LMP1 oncogene, associated with aggressive behavior in NPC CAO and NPC 1510, occur at a particular localization and confer a proliferative phenotype to lymphoid cells in HD.


2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096933
Author(s):  
Yun-peng Bai ◽  
Bo-chen Yao ◽  
Mei Wang ◽  
Xian-kun Liu ◽  
Xiao-long Zhu ◽  
...  

Background Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. Methods This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein–protein interaction network and a hub gene network. Results Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes ( KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson’s correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 < area under the curve ≤1). Conclusion BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.


Sign in / Sign up

Export Citation Format

Share Document