Dataset Information

Prioritizing cancer-related microRNAs by integrating microRNA and mRNA datasets.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of target genes, and they are involved in cancer initiation and progression. Even though many cancer-related miRNAs were identified, their functional impact may vary, depending on their effects on the regulation of other miRNAs and genes. In this study, we propose a novel method for the prioritization of candidate cancer-related miRNAs that may affect the expression of other miRNAs and genes across the entire biological network. For this, we propose three important features: the average expression of a miRNA in multiple cancer samples, the average of the absolute correlation values between the expression of a miRNA and expression of all genes, and the number of predicted miRNA target genes. These three features were integrated using order statistics. By applying the proposed approach to four cancer types, glioblastoma, ovarian cancer, prostate cancer, and breast cancer, we prioritized candidate cancer-related miRNAs and determined their functional roles in cancer-related pathways. The proposed approach can be used to identify miRNAs that play crucial roles in driving cancer development, and the elucidation of novel potential therapeutic targets for cancer treatment.

SUBMITTER: Jin D

PROVIDER: S-EPMC5062133 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Prioritizing cancer-related microRNAs by integrating microRNA and mRNA datasets.

Jin Daeyong D Lee Hyunju H

Scientific reports 20161013

MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of target genes, and they are involved in cancer initiation and progression. Even though many cancer-related miRNAs were identified, their functional impact may vary, depending on their effects on the regulation of other miRNAs and genes. In this study, we propose a novel method for the prioritization of candidate cancer-related miRNAs that may affect the expression of other miRNAs and genes across the entire biological netwo ...[more]

PMID: 27734929

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Project description:Identifying disease-associated microRNAs (disease miRNAs) contributes to the understanding of disease pathogenesis. Most previous computational biology studies focused on multiple kinds of connecting edges of miRNAs and diseases, including miRNA-miRNA similarities, disease-disease similarities, and miRNA-disease associations. Few methods exploited the node attribute information related to miRNA family and cluster. The previous methods do not completely consider the sparsity of node attributes. Additionally, it is challenging to deeply integrate the node attributes of miRNAs and the similarities and associations related to miRNAs and diseases. In the present study, we propose a novel method, known as MDAPred, based on nonnegative matrix factorization to predict candidate disease miRNAs. MDAPred integrates the node attributes of miRNAs and the related similarities and associations of miRNAs and diseases. Since a miRNA is typically subordinate to a family or a cluster, the node attributes of miRNAs are sparse. Similarly, the data for miRNA and disease similarities are sparse. Projecting the miRNA and disease similarities and miRNA node attributes into a common low-dimensional space contributes to estimating miRNA-disease associations. Simultaneously, the possibility that a miRNA is associated with a disease depends on the miRNA's neighbour information. Therefore, MDAPred deeply integrates projections of multiple kinds of connecting edges, projections of miRNAs node attributes, and neighbour information of miRNAs. The cross-validation results showed that MDAPred achieved superior performance compared to other state-of-the-art methods for predicting disease-miRNA associations. MDAPred can also retrieve more actual miRNA-disease associations at the top of prediction results, which is very important for biologists. Additionally, case studies of breast, lung, and pancreatic cancers further confirmed the ability of MDAPred to discover potential miRNA-disease associations.

Project description:MotivationMicroRNAs (miRNAs) play important roles in general biological processes and diseases pathogenesis. Identifying miRNA target genes is an essential step to fully understand the regulatory effects of miRNAs. Many computational methods based on the sequence complementary rules and the miRNA and mRNA expression profiles have been developed for this purpose. It is noted that there have been many sequence features of miRNA targets available, including the context features of the target sites, the thermodynamic stability and the accessibility energy for miRNA-mRNA interaction. However, most of current computational methods that combine sequence and expression information do not effectively integrate full spectrum of these features; instead, they perceive putative miRNA-mRNA interactions from sequence-based prediction as equally meaningful. Therefore, these sequence features have not been fully utilized for improving miRNA target prediction.ResultsWe propose a novel regularized regression approach that is based on the adaptive Lasso procedure for detecting functional miRNA-mRNA interactions. Our method fully takes into account the gene sequence features and the miRNA and mRNA expression profiles. Given a set of sequence features for each putative miRNA-mRNA interaction and their expression values, our model quantifies the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature to predicting functional miRNA-mRNA interactions. By applying our model to the expression datasets from two cancer studies, we have demonstrated our prediction results have achieved better sensitivity and specificity and are more biologically meaningful compared with those based on other methods.Availability and implementationThe source code is available at: http://nba.uth.tmc.edu/homepage/liu/miRNALasso.Supplementary informationSupplementary data are available at Bioinformatics online.ContactYin.Liu@uth.tmc.edu.

Project description:BackgroundSince there are inextricably connections among molecules in the biological networks, it would be a more efficient and accurate research strategy to screen microRNA (miRNA) markers combining with miRNA-mRNA regulatory networks. The independent regulation mode is more "fragile" and "influential" than the co-regulation mode. miRNAs can be used as biomarkers if they can independently regulate hub genes with important roles in the PPI network, simultaneously the expression products of the regulated hub genes play important roles in the signaling pathways of related tissue diseases.MethodsWe collected miRNA expression of non-small cell lung cancer (NSCLC) from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Volcano plot and signal-to-noise ratio (SNR) methods were used to obtain significant differentially expressed (SDE) miRNAs from the TCGA database and GEO database, respectively. A human miRNA-mRNA regulatory network was constructed and the number of genes uniquely targeted (NOG) by a certain miRNA was calculated. The area under the curve (AUC) values were used to screen for clinical sensitivity and specificity. The candidate markers were obtained using the criteria of the top five maximum AUC values and NOG ≥ 3. The protein-protein interaction (PPI) network was constructed and independently regulated hub genes were obtained. Gene Ontology (GO) analysis and KEGG pathway analysis were used to identify genes involved in cancer-related pathways. Finally, the miRNA which can independently regulate a hub gene and the hub gene can participate in an important cancer-related pathway was considered as a biomarker. The AUC values and gene expression profile analysis from two external GEO datasets as well as literature validation were used to verify the screening capability and reliability of this marker.ResultsFifteen SDE miRNAs in lung cancer were obtained from the intersection of volcano plot and SNR based on the GEO database and the TCGA database. Five miRNAs with the top five maximum AUC values and NOG ≥ 3 were screened out. A total of 61 hub genes were obtained from the PPI network. It was found that the hub gene GTF2F2 was independently regulated by miR-708-5p. Further pathway analysis indicated that GTF2F2 participates in protein expression by binding with polymerase II, and it can regulate transcription and accelerate tumor growth. Hence, miR-708-5p could be used as a biomarker. The good screening capability and reliability of miR-708-5p as a lung cancer marker were confirmed by AUC values and gene expression profiling of external datasets, and experimental literature. The potential mechanism of miR-708-5p was proposed.ConclusionsThis study proposes a new idea for lung cancer marker screening by integrating microRNA expression, regulation network and signal pathway. miR-708-5p was identified as a biomarker using this novel strategy. This study may provide some help for cancer marker screening.

Dataset Information

Prioritizing cancer-related microRNAs by integrating microRNA and mRNA datasets.

Publications

Prioritizing cancer-related microRNAs by integrating microRNA and mRNA datasets.

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