DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions

Vlachos, Ioannis S.; Paraskevopoulou, Maria D.; Karagkouni, Dimitra; Γεωργακίλας, Γεώργιος; Vergoulis, Thanasis; Kanellos, Ilias; Anastasopoulos, I.; Maniou, Sofia; Karathanou, Konstantina; Kalfakakou, Despina; Fevgas, Athanasios; Dalamagas, Theodore; Hatzigeorgiou, Artemis G.

doi:10.1093/nar/gku1215

Cited by 698 publications

(579 citation statements)

References 30 publications

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“…P<0.05 was considered to indicate a statistically significant difference. DIANA-TarBase v7.0 and DIANA-miRPath v3.0 bioinformatic tools were used to identify overlapped target genes of the miRNAs of interest (14,15).…”

Section: Methodsmentioning

confidence: 99%

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

et al. 2017

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Abstract. Attributing to their pathophysiological role and stability in biological samples, microRNAs (miRNAs) have the potential to become valuable predictive markers for non-small cell lung cancer (NSCLC). Samples of biopsy tissue constitute suitable material for miRNA profiling with the aim of predicting the effect of palliative chemotherapy. The present study group included 81 patients (74 males, 7 females, all smokers or former smokers) with the squamous cell carcinoma (SCC) histological subtype of NSCLC at a late stage (3B or 4). All patients received palliative chemotherapy based on platinum derivatives in combination with paclitaxel or gemcitabine. The expression of 17 selected miRNAs was measured by reverse transcription-quantitative polymerase chain reaction in tumor tissue macrodissected from formalin-fixed paraffin-embedded (FFPE) tissue samples. To predict the effect of palliative chemotherapy, the association between gene expression levels and overall survival (OS) time was analyzed. From the 17 miRNAs of interest, low expression levels of miR-342 and high expression levels of miR-34a and miR-224 were associated with a reduced OS time in subgroups of patients based on smoking status and treatment modality. Using cluster analysis, associations between combinations of miR-34a, -224 and -342 expression levels with patient survival were identified. The present study revealed that patients with the simultaneous high expression of miR-224 and -342 had a similar prognostic outcome to those with the low expression of miR-224 and -342, which was significantly reduced, compared with patients exhibiting high expression of either miR-224 or miR-342 with low expression of the other. We hypothesize that the effect of a particular miRNA is dependent on the expression level of other members of the miRNA network. This finding appears to complicate survival analyses based on individual miRNAs as markers. In conclusion, the present study provides evidence that specific miRNAs were associated with OS time, which may be candidate predictors for the effectiveness of palliative treatment in SCC lung cancer patients. This objective can be better achieved by combining more markers together than by using individual miRNAs.

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Section: Methodsmentioning

confidence: 99%

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

et al. 2017

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“…To obtain biological interpretation from altered miRNAs, target mRNAs were obtained from the experimentally-derived mRNA target (Vlachos et al, 2015). First, to allow a more reliable biological interpretation (avoiding false positive findings), a foldchange threshold was included (Mestdagh et al, 2009): only the differentially expressed miRNAs with log2 fold-changes exceeding 0.33 (those with at least 1.25 fold-changes, in addition to the statistical significance) were included in the analysis.…”

Section: Mirna Analysismentioning

confidence: 99%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

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ratory animals -to reduce the number of animals, to refine the design of procedures such that pain and distress are minimized, and to replace animal models with alternative methods and lower organisms when possible (Doke and Dhawale, 2015). In this regard, the capability to preserve human respiratory cells in culture provides a tool not only to generate mechanistic data, but also to improve the predicted effects of exposure hazard through inhalation in humans. An emphasis on assessment studies using human-derived in vitro culture systems will reduce the problems that are inherent to interspecies translatability (Manuppello and Sullivan, 2015).In vitro toxicology approaches have evolved from focusing on the molecular changes within a cell to understanding the toxicity-related mechanisms (cell-cell interactions) in models IntroductionMechanistic investigation of the impact of exposure on the lower airway remains challenging because access to lung tissues is limited. Although biopsy samples can be obtained from patients/donors for mechanistic studies of exposure-induced injury, a biopsy procedure is invasive and there are related ethical concerns (Peppercorn, 2013). Alternatively, animal studies allow the collection of biological samples from various animal models of human diseases. However, biological responses can vary among animal species, and findings obtained from animal studies may not apply to humans. Alternatives to animal testing have been proposed to overcome these drawbacks, including the 3Rs strategy -reduction, refinement, and replacement of labo- Research SummaryIn vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21 st Century -a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impa...

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“…We used the target gene prediction software DIANATarBase (14), Targetscan (http://www.targetscan.org) and PicTar (http://pictar.mdc-berlin.de/) to forecast several potential target genes of miR-181a.…”

Section: Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Huang¹,

Zhao²,

Weng³

et al. 2016

International Journal of Oncology

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Abstract. To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, Gene Ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.

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DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions

Cited by 698 publications

References 30 publications

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

Predictive relevance of miR‑34a, miR‑224 and miR‑342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

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