scholarly journals VECTOR: An Integrated Correlation Network Database for the Identification of CeRNA Axes in Uveal Melanoma

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1004
Author(s):  
Cristina Barbagallo ◽  
Antonio Di Maria ◽  
Adriana Alecci ◽  
Davide Barbagallo ◽  
Salvatore Alaimo ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
The Cancer Genome Atlas ◽  
Correlation Network ◽  
Rna Molecules ◽  
Network Database ◽  
Antisense Sequence ◽  
Cancer Genome Atlas ◽  
Non Coding Rnas ◽  
Competitive Endogenous Rna ◽  
Rna Signaling

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and, although its genetic background has been extensively studied, little is known about the contribution of non-coding RNAs (ncRNAs) to its pathogenesis. Indeed, its competitive endogenous RNA (ceRNA) regulatory network comprising microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs has been insufficiently explored. Thanks to UM findings from The Cancer Genome Atlas (TCGA), it is now possible to statistically elaborate these data to identify the expression relationships among RNAs and correlative interaction data. In the present work, we propose the VECTOR (uVeal mElanoma Correlation NeTwORk) database, an interactive tool that identifies and visualizes the relationships among RNA molecules, based on the ceRNA model. The VECTOR database contains: i) the TCGA-derived expression correlation values of miRNA-mRNA, miRNA-lncRNA and lncRNA-mRNA pairs combined with predicted or validated RNA-RNA interactions; ii) data of sense-antisense sequence overlapping; iii) correlation values of Transcription Factor (TF)-miRNA, TF-lncRNA, and TF-mRNA pairs associated with ChiPseq data; iv) expression data of miRNAs, lncRNAs and mRNAs both in UM and physiological tissues. The VECTOR web interface can be queried, by inputting the gene name, to retrieve all the information about RNA signaling and visualize this as a graph. Finally, VECTOR provides a very detailed picture of ceRNA networks in UM and could be a very useful tool for researchers studying RNA signaling in UM. The web version of Vector is freely available at the URL reported at the end of the Introduction.

scholarly journals Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 227 ◽  
Author(s):  
Qi Wan ◽  
Xuan Sang ◽  
Lin Jin ◽  
Zhichong Wang
Keyword(s):  
Alternative Splicing ◽  
Uveal Melanoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Correlation Network ◽  
Support Vector ◽  
Cancer Genome Atlas ◽  
Alternative Splicing Events ◽  
Genome Atlas

Growing evidence has revealed that abnormal alternative splicing (AS) events are closely related to carcinogenic processes. However, the comprehensive study on the prognostic value of splicing events involved in uveal melanoma (UM) is still lacking. Therefore, splicing data of 80 UM patients were obtained from the Cancer Genome Atlas (TCGA) SpliceSeq and RNA sequence data of UM and patient clinical features were downloaded from the Cancer Genome Atlas (TCGA) database to identify survival related splicing events in UM. As a result, a total of 37996 AS events of 17911 genes in UM were detected, among which 5299 AS events of 3529 genes were significantly associated with UM patients’ survival. Functional enrichment analysis revealed that this survival related splicing genes are corelated with mRNA catabolic process and ribosome pathway. Based on survival related splicing events, seven types of prognostic markers and the final overall prognostic signature could independently predict the overall survival of UM patients. Finally, an 11 spliced gene was identified in the final signature. On the basis of these 11 genes, we constructed a Support Vector Machine (SVM) classifier and evaluated it with leave-one-out cross-validation. The results showed that the 11 genes could determine short- and long-term survival with a predicted accuracy of 97.5%. Besides, the splicing factors and alternative splicing events correlation network was constructed to serve as therapeutic targets for UM treatment. Thus, our study depicts a comprehensive landscape of alternative splicing events in the prognosis of UM. The correlation network and associated pathways would provide additional potential targets for therapy and prognosis.

scholarly journals Identification of a putative competitive endogenous RNA network for lung adenocarcinoma using TCGA datasets

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6809 ◽  
Author(s):  
Yuanyong Wang ◽  
Tong Lu ◽  
Yang Wo ◽  
Xiao Sun ◽  
Shicheng Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Regulatory Networks ◽  
Sequence Similarity ◽  
The Cancer Genome Atlas ◽  
Potential Significance ◽  
Cancer Genome Atlas ◽  
Non Coding Rnas ◽  
Online Prediction ◽  
Genome Atlas ◽  
Competitive Endogenous Rna

The mechanisms underlying the oncogenesis and progression of lung adenocarcinoma (LUAD) are currently unclear. The discovery of competitive endogenous RNA (ceRNA) regulatory networks has provided a new direction for the treatment and prognosis of patients with LUAD. However, the mechanism of action of ceRNA in LUAD remains elusive. In the present study, differentially expressed mRNAs, microRNAs (miRs) and long non-coding RNAs from the cancer genome atlas database were screened. CeRNAs for LUAD were then identified using online prediction software. Among the ceRNAs identified, family with sequence similarity 83 member A (FAM83A), miR-34c-5p, KCNQ1OT1 and FLJ26245 were observed to be significantly associated with the overall survival of patients with LUAD. Of note, FAM83A has potential significance in drug resistance, and may present a candidate biomarker for the prognosis and treatment of patients with LUAD.

scholarly journals Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma

2020 ◽  
Vol 9 (2) ◽  
pp. 411 ◽  
Author(s):  
Feng Liu-Smith ◽  
Yunxia Lu
Keyword(s):  
Overall Survival ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Copy Number Variations ◽  
The Cancer Genome Atlas ◽  
Small Subset ◽  
Mrna Levels ◽  
Cancer Genome Atlas

Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes.

scholarly journals Abnormally expressed JunB transactivated by IL-6/STAT3 signaling promotes uveal melanoma aggressiveness via epithelial–mesenchymal transition

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Chaoju Gong ◽  
Jie Shen ◽  
Zejun Fang ◽  
Lei Qiao ◽  
Ruifang Feng ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Epithelial Marker ◽  
Cancer Genome Atlas

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell–cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial–mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis.

scholarly journals Characterization of ceRNA network to reveal potential prognostic biomarkers in triple-negative breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7522 ◽  
Author(s):  
Xiang Song ◽  
Chao Zhang ◽  
Zhaoyun Liu ◽  
Qi Liu ◽  
Kewen He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Quantitative Polymerase Chain Reaction ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Non Coding Rnas

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan–Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.

scholarly journals The Cancer Genome Atlas Project: An Integrated Molecular View of Uveal Melanoma

Ophthalmology ◽  
2018 ◽  
Vol 125 (8) ◽  
pp. 1139-1142 ◽  
Author(s):  
Martine J. Jager ◽  
Niels J. Brouwer ◽  
Bita Esmaeli
Keyword(s):  
Uveal Melanoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

The Microenvironment Combining with Immune Infiltration of Uveal Melanoma

2021 ◽  
Author(s):  
Daowei Zhang ◽  
Jiawen Wu ◽  
Jihong Wu ◽  
Shenghai Zhang
Keyword(s):  
Uveal Melanoma ◽  
Immune Cells ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Malignant Tumours ◽  
Cancer Genome Atlas ◽  
Key Genes ◽  
Low Expression

Abstract Background: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although immunotherapy provided novel options in the disease's progression, it only benefits a minority of patients. The understanding of the UM microenvironment and the potential therapeutic targets in the microenvironment is still undefined. We aimed to propose a novel classification of UM microenvironment to identify ideal biomarkers for prognosis and potential targets for effective immunotherapy.Methods: In this study, we obtained the gene expression profile of 80 UM patients from the Cancer Genome Atlas (TCGA) and calculated immune/stromal scores based on the Estimation of stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm dividing patients into the high- and low-expression groups. Then, 1024 immune-related differently expressed genes (DEGs) were selected in total following the annotation and enrichment analysis and key genes were screened by PPI network. Consequently, we conducted CIBERSORT algorithm and TIMER database to analyses the correlation between key genes and immune cells as well as utilized GeneCards database to analyses the correlation between key genes and the disease. Additionally, GSVA was performed to enrich the nonparametric and unsupervised signaling pathways of key genes and the drug sensitivity of them were predicted.Results: Based on high- and low-expression groups, we found that there were 888 up-regulated DEGs and 126 down-regulated DEGs in total, which were mainly enriched in 4 pathways in GO and 3 pathways in KEGG. Combining with the 10 genes screened by PPI, KM-plot showed that B2M and HLA-B were significantly affected the survival of UM patients. Among 22 immune cells, B2M and HLA-B were mainly corelated with 11 of them. GSVA results revealed 42 pathways significantly enriched of B2M while 41 pathways enriched of HLA-B. Finally, we predicted the Paclitaxel as the hopefully treatment for HLA-B.Conclusions: Our study not only understands deeper of fundamental biological features of microenvironment but also with potential therapeutic targets of UM.

Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D

Ophthalmology ◽  
2019 ◽  
Vol 126 (10) ◽  
pp. 1445-1453 ◽  
Author(s):  
Pornpattana Vichitvejpaisal ◽  
Lauren A. Dalvin ◽  
Mehdi Mazloumi ◽  
Kathryn G. Ewens ◽  
Arupa Ganguly ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Uveal Melanoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Multi-Platform Omics Analysis for Identification of Molecular Characteristics and Therapeutic Targets of Uveal Melanoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong Joon Kim ◽  
Seo Jin Park ◽  
Kyung Joo Maeng ◽  
Sung Chul Lee ◽  
Christopher Seungkyu Lee
Keyword(s):  
Uveal Melanoma ◽  
Copy Number ◽  
Checkpoint Inhibitors ◽  
Therapeutic Targets ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Synthetic Lethal ◽  
Whole Exome ◽  
Cancer Genome Atlas ◽  
Sirna Library

AbstractCurrently, there is no effective treatment for metastatic uveal melanoma (UVM). Here, we aimed to identify the mechanism involving intrinsic chemoresistance of metastatic UVM and the relevant therapeutic targets for UVM. We analyzed cohorts of 80 and 67 patients with primary UVM and skin cutaneous melanoma (SKCM), respectively, using The Cancer Genome Atlas dataset. Mutational burdens identified by whole exome sequencing were significantly lower in UVM than in SKCM patients. COSMIC mutational signature analysis identified that most of the mutations in UVM patients (>90%) were associated with spontaneous deamination of 5-methylcytosine or defective mismatch repair. Transcriptome analysis revealed that the MYC signature was more enriched in UVM patients, as compared to SKCM patients. Fifty-nine (73.8%) of 80 UVM patients showed gains in MYC copy number, and a high MYC copy number was associated with aggressive clinicopathological features of tumors and poor survival. Kinome-wide siRNA library screening identified several therapeutic targets, reported as synthetic lethal targets for MYC-addicted cancers. Notably, UVM cell lines showed high susceptibility to a WEE1 inhibitor (MK-1775; adavosertib) at a clinically tolerable dose. Overall, our study identified high MYC activity in UVM, and suggested G2/M checkpoint inhibitors as effective therapeutic targets for UVM.

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