miRecords: an integrated resource for microRNA-target interactions

Xiao, Feifei; Zuo, Zhixiang; Cai, Guoshuai; Kang, Shuli; Gao, Xiaolian; Li, Tongbin

doi:10.1093/nar/gkn851

Cited by 1,329 publications

(1,131 citation statements)

References 59 publications

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“…Human miRNAs and their associated targets were downloaded from 3 high-quality online miRNA reference databases, which store manual collections of experimentally supported miRNA targets, miRecords (24), miRTarBase (25) and TarBase 6.0 (26). In addition, all pathways and associated genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (27).…”

Section: Mirna-target Gene and Kegg Pathway Data Collectionmentioning

confidence: 99%

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Xue

Liu

et al. 2015

International Journal of Molecular Medicine

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Abstract. The present study aimed to explore potential molecular targets and gain further insights into the mechanism of intervertebral disc degeneration (IDD) progression. Microarray datasets of GSE19943, GSE15227 and GSE34095 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in 3 IDD specimens compared with 3 controls in GSE34095, DEGs in 7 grade III and 3 grade IV samples compared with 5 grade II samples in GSE19943, and differentially expressed miRNAs in 3 degenerated samples compared with 3 controls in GSE15227 were screened. Grade III-and IV-specific networks were constructed and grade-specific genes were extracted. The network features were analyzed, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis of grade-specific genes and DEGs identified in GSE34095. Furthermore, miRNA-pathway interactions were analyzed using Fisher's exact test. Tumor protein p53 (TP53) was a hub gene in the grade III-specific network and ubiquitin C (UBC) was identified to be a hub gene in the grade IV-specific network. Six significant features were identified by grade-specific network topology analysis. Grade-specific genes and DEGs were involved in different GO terms and pathways. Differentially expressed miRNAs were identified to participate in 35 pathways, among which 6 pathways were significantly enriched by DEGs, including apoptosis. The present study identified that key genes (TP53 and UBC) and miR-129-5p may participate in the mechanism of IDD progression. Thus, they may be potential therapeutic targets for IDD.

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Section: Mirna-target Gene and Kegg Pathway Data Collectionmentioning

confidence: 99%

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Xue

Liu

et al. 2015

International Journal of Molecular Medicine

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“…To investigate this idea, we identified putative targets of each miRNA using miRecords, 31 implemented with a stringent cut-off to retrieve only those genes that were predicted by at least 4 different target prediction programs (Supporting Information Table 3). Key pathways in prostate cancer, including ''Wnt signaling,'' 32 ''MAPK signaling,'' 28 ''p53 signaling,'' 28 ''ErbB signaling,'' 33 ''TGF-beta signaling'' 34 and ''Prostate cancer'', were significantly enriched in the combined gene set putatively targeted by hsa-miR-141 and hsa-miR-375 (Supporting Information Table 4).…”

Section: Circulating Mirna Markers Of Prostate Cancer May Target Keymentioning

confidence: 99%

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Selth

Townley

Gillis

et al. 2011

Intl Journal of Cancer

177

155

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Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration-resistant prostate cancer (mCRPC; n 5 25) or healthy men (n 5 25). Four miRNAs altered in mice, mmumiR-141, mmu-miR-298, mmu-miR-346 and mmu-miR-375, were also found to be at differential levels in the serum of men with mCRPC. Three of these (hsa-miR-141, hsa-miR-298 and hsa-miR-375) were upregulated in prostate tumors compared with normal prostate tissue, suggesting that they are released into the blood as disease progresses. Moreover, the intra-tumoral expression of hsa-miR-141 and hsa-miR-375 were predictors of biochemical relapse after surgery. This study is the first to demonstrate that specific serum miRNAs are common between human prostate cancer and a mouse model of the disease, highlighting the potential of such models for the discovery of novel biomarkers.Prostate cancer is the most commonly diagnosed non-skin malignancy in men in Western countries, constituting up to 25% of all male cancer diagnoses and 9% of cancer deaths among men in the USA and Europe. 1,2 The widespread use of serum prostate specific antigen (PSA) testing along with increasing public awareness of prostate cancer has resulted in a significant increase in the proportion of patients with clinically localized tumors at the time of diagnosis who likely will not die of the disease. 3 Localized prostate cancers exhibit high levels of genetic, biological and clinical heterogeneity, 4,5 and current prognostic tools (based upon clinicopathologic parameters) are imperfect predictors of disease course. New molecular markers are urgently required to better predict the likely outcome and behavior of individual cancers. microRNAs (miRNAs) are small RNA molecules of 21-23nt that bind with imperfect complementarity to sequences in specific mRNA targets and typically silence their expression by translational inhibition or mRNA decay. miRNAs are estimated to regulate the expression of greater than 60% of all protein-coding genes 6 and, as such, play vital roles in all aspects of normal physiology. Given their biological importance, it is not surprising that miRNA expression is frequently dysregulated in human cancer. 7 Accumulating evidence suggests that miRNAs can contribute to tumorigenesis either by directly modulating oncogenic or tumor suppressor pathways (oncomirs and tumor suppressor miRNAs, respectively) and/or being regulated by oncogenes or tumor suppressor genes. 8 Several characteristics of miRNAs make them ideal biomarkers for...

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“…In the picture, dashed lines refer to indirect relations, full lines to direct ones (see also the legend inset). Black circled molecules of Figure 7b represent known miR-21 targets (Xiao et al, 2009) whereas double black circled ones are predicted targets present in downregulated genes list (see Supplementary Methods). The network has one major hub nodes, the tumor suppressor p53, which is downregulated in this experiment.…”

Section: Regulation Of Mir-21 By Ras and Its Role In Cancer D Frezzetmentioning

confidence: 99%

Upregulation of miR-21 by Ras in vivo and its role in tumor growth

et al. 2010

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miR-21 is a microRNA (miRNA) frequently overexpressed in human cancers. Here we show that miR-21 is upregulated both in vitro and in vivo by oncogenic Ras, thus linking this miRNA to one of the most frequently activated oncogenes in human cancers. Ras regulation of miR-21 occurs with a delayed kinetic and requires at least two Ras downstream pathways. A screen of human thyroid cancers and non-small-cell lung cancers for the expression of miR-21 reveals that it is overexpressed mainly in anaplastic thyroid carcinomas, the most aggressive form of thyroid cancer, whereas in lung its overexpression appears to be inversely correlated with tumor progression. We also show that a LNA directed against miR-21 slows down tumor growth in mice. Consistently, a search for mRNAs downregulated by miR-21 shows an enrichment for mRNAs encoding cell cycle checkpoints regulators, suggesting an important role for miR-21 in oncogenic Ras-induced cell proliferation.

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miRecords: an integrated resource for microRNA-target interactions

Cited by 1,329 publications

References 59 publications

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

Upregulation of miR-21 by Ras in vivo and its role in tumor growth

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