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1.
Trends Genet ; 36(7): 461-463, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32544447

RESUMO

Since 2002, published miRNAs have been collected and named by the online repository miRBase. However, with 11 000 annual publications this has become challenging. Recently, four specialized miRNA databases were published, addressing particular needs for diverse scientific communities. This development provides major opportunities for the future of miRNA annotation and nomenclature.

2.
Nature ; 582(7813): 545-549, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32499655

RESUMO

Animals sense the environment through pathways that link sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space in which visual stimuli excite a neuron1. The visual system also uses visual context-the visual scene surrounding a stimulus-to predict the content of the stimulus2, and accordingly, neurons have been identified that are excited by stimuli outside their ffRF3-8. However, the mechanisms that generate excitation to stimuli outside the ffRF are unclear. Here we show that feedback projections onto excitatory neurons in the mouse primary visual cortex generate a second receptive field that is driven by stimuli outside the ffRF. The stimulation of this feedback receptive field (fbRF) elicits responses that are slower and are delayed in comparison with those resulting from the stimulation of the ffRF. These responses are preferentially reduced by anaesthesia and by silencing higher visual areas. Feedback inputs from higher visual areas have scattered receptive fields relative to their putative targets in the primary visual cortex, which enables the generation of the fbRF. Neurons with fbRFs are located in cortical layers that receive strong feedback projections and are absent in the main input layer, which is consistent with a laminar processing hierarchy. The observation that large, uniform stimuli-which cover both the fbRF and the ffRF-suppress these responses indicates that the fbRF and the ffRF are mutually antagonistic. Whereas somatostatin-expressing inhibitory neurons are driven by these large stimuli, inhibitory neurons that express parvalbumin and vasoactive intestinal peptide have mutually antagonistic fbRF and ffRF, similar to excitatory neurons. Feedback projections may therefore enable neurons to use context to estimate information that is missing from the ffRF and to report differences in stimulus features across visual space, regardless of whether excitation occurs inside or outside the ffRF. By complementing the ffRF, the fbRF that we identify here could contribute to predictive processing.

3.
Cells ; 9(6)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531952

RESUMO

Neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration.

4.
RNA Biol ; : 1-11, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32456538

RESUMO

MicroRNAs are regulators of gene expressionand may be key markers in liquid biopsy.Early diagnosis is an effective means to increase patients' overall survival. We generated genome-wide miRNA profiles from serum of patients and controls from the population-based Janus Serum Bank (JSB) and analysed them by bioinformatics and artificial intelligence approaches. JSB contains sera from 318,628 originally healthy persons, more than 96,000 of whom developed cancer. We selected 210 serum samples from patients with lung, colon or breast cancer at three time points prior to diagnosis (up to 32 years prior to diagnosis with median 5 years interval between TPs), one time-point after diagnosis and from individually matched controls. The controls were matched on age and year of all pre-diagnostic sampling time-points for the corresponding case. Using ANOVA we report 70 significantly deregulated markers (adjusted p-value<0.05). The driver for the significance was the diagnostic time point (miR-575, miR-6821-5p, miR-630 with adjusted p-values<10-10). Further, 91miRNAs were differently expressed in pre-diagnostic samples as compared to controls (nominal p < 0.05). Self-organized maps (SOMs)indicated larges effects in lung cancer samples while breast cancer samples showed the least pronounced changes. SOMsalsohighlighted cancer and time point specific miRNA dys-regulation. Intriguingly, a detailed breakdown of the results highlighted that 51% of all miRNAs were highly specific, either for a time-point or a cancer entity. Pathway analysis highlighted 12 pathways including Hipo signalling and ABC transporters.Our results indicate that tumours may be indicated by serum miRNAs decades prior the clinical manifestation.

5.
Nucleic Acids Res ; 48(W1): W268-W274, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32356893

RESUMO

Arm selection, the preferential expression of a 3' or 5' mature microRNA (miRNA), is a highly dynamic and tissue-specific process. Time-dependent expression shifts or switches between the arms are also relevant for human diseases. We present miRSwitch, a web server to facilitate the analysis and interpretation of arm selection events. Our species-independent tool evaluates pre-processed small non-coding RNA sequencing (sncRNA-seq) data, i.e. expression matrices or output files from miRNA quantification tools (miRDeep2, miRMaster, sRNAbench). miRSwitch highlights potential changes in the distribution of mature miRNAs from the same precursor. Group comparisons from one or several user-provided annotations (e.g. disease states) are possible. Results can be dynamically adjusted by choosing from a continuous range of highly specific to very sensitive parameters. Users can compare potential arm shifts in the provided data to a human reference map of pre-computed arm shift frequencies. We created this map from 46 tissues and 30 521 samples. As case studies we present novel arm shift information in a Alzheimer's disease biomarker data set and from a comparison of tissues in Homo sapiens and Mus musculus. In summary, miRSwitch offers a broad range of customized arm switch analyses along with comprehensive visualizations, and is freely available at: https://www.ccb.uni-saarland.de/mirswitch/.

6.
Nucleic Acids Res ; 48(W1): W521-W528, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32374865

RESUMO

Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, the same statistical principles are now available for all omics types. In 2016, we published the miRNA enrichment analysis and annotation tool (miEAA) for human precursor and mature miRNAs. Here, we present miEAA 2.0, supporting miRNA input from ten frequently investigated organisms. To facilitate inclusion of miEAA in workflow systems, we implemented an Application Programming Interface (API). Users can perform miRNA set enrichment analysis using either the web-interface, a dedicated Python package, or custom remote clients. Moreover, the number of category sets was raised by an order of magnitude. We implemented novel categories like annotation confidence level or localisation in biological compartments. In combination with the miRBase miRNA-version and miRNA-to-precursor converters, miEAA supports research settings where older releases of miRBase are in use. The web server also offers novel comprehensive visualizations such as heatmaps and running sum curves with background distributions. We demonstrate the new features with case studies for human kidney cancer, a biomarker study on Parkinson's disease from the PPMI cohort, and a mouse model for breast cancer. The tool is freely accessible at: https://www.ccb.uni-saarland.de/mieaa2.

7.
Nucleic Acids Res ; 48(W1): W515-W520, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32379325

RESUMO

We present GeneTrail 3, a major extension of our web service GeneTrail that offers rich functionality for the identification, analysis, and visualization of deregulated biological processes. Our web service provides a comprehensive collection of biological processes and signaling pathways for 12 model organisms that can be analyzed with a powerful framework for enrichment and network analysis of transcriptomic, miRNomic, proteomic, and genomic data sets. Moreover, GeneTrail offers novel workflows for the analysis of epigenetic marks, time series experiments, and single cell data. We demonstrate the capabilities of our web service in two case-studies, which highlight that GeneTrail is well equipped for uncovering complex molecular mechanisms. GeneTrail is freely accessible at: http://genetrail.bioinf.uni-sb.de.

8.
PLoS One ; 15(4): e0231402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271829

RESUMO

BACKGROUND: Turner syndrome (TS) is a chromosomal disorder, in which a female is partially or entirely missing one of the two X chromosomes, with a prevalence of 1:2500 live female births. The present study aims to identify a circulating microRNA (miRNA) signature for TS patients with and without congenital heart disease (CHD). METHODS: Microarray platform interrogating 2549 miRNAs were used to detect the miRNA abundance levels in the blood of 33 TS patients and 14 age-matched healthy volunteer controls (HVs). The differentially abundant miRNAs between the two groups were further validated by RT-qPCR. RESULTS: We identified 60 differentially abundant miRNA in the blood of TS patients compared to HVs, from which, 41 and 19 miRNAs showed a higher and a lower abundance levels in TS patients compared to HVs, respectively. RT-qPCR confirmed the significantly higher abundance levels of eight miRNAs namely miR-374b-5p, miR-199a-5p, miR-340-3p, miR-125b-5p, miR-30e-3p, miR-126-3p, miR-5695, and miR-26b-5p in TS patients as compared with the HVs. The abundance level of miR-5695 was higher in TS patients displaying CHD as compared to TS patients without CHD (p = 0.0265; log2-fold change 1.99); whereas, the abundance level of miR-126-3p was lower in TS patients with congenital aortic valve disease (AVD) compared to TS patients without BAV (p = 0.0139, log2-fold change 1.52). The clinical feature statistics revealed that miR-126-3p had a significant correlation with sinotubular junction Z-score (r = 0.42; p = 0.0154). CONCLUSION: The identified circulating miRNAs signature for TS patients with manifestations associated with cardiovascular diseases provide new insights into the molecular mechanism of TS that may guide the development of novel diagnostic approaches.

9.
J Mol Cell Cardiol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32305360

RESUMO

BACKGROUND: Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on reported symptoms in the troponin-negative group. In this study, we investigated genome-wide miRNA levels in a prospective cohort of patients with clinically suspected ACS and determined their diagnostic value by applying an in silico neural network. METHODS: PAXgene blood and serum samples were drawn and hsTnT was measured in patients at initial presentation to our Chest-Pain Unit. After clinical and diagnostic workup, patients were adjudicated by senior cardiologists in duty to their final diagnosis: STEMI, NSTEMI, unstable angina pectoris and non-ACS patients. ACS patients and a cohort of healthy controls underwent deep transcriptome sequencing. Machine learning was implemented to construct diagnostic miRNA classifiers. RESULTS: We developed a neural network model which incorporates 34 validated ACS miRNAs, showing excellent classification results. By further developing additional machine learning models and selecting the best miRNAs, we achieved an accuracy of 0.96 (95% CI 0.96-0.97), sensitivity of 0.95, specificity of 0.96 and AUC of 0.99. The one-point hsTnT value reached an accuracy of 0.89, sensitivity of 0.82, specificity of 0.96, and AUC of 0.96. CONCLUSIONS: Here we show the concept of neural network based biomarkers for ACS. This approach also opens the possibility to include multi-modal data points to further increase precision and perform classification of other ACS differential diagnoses.

10.
Respir Res ; 21(1): 67, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164736

RESUMO

BACKGROUND: The use of electronic cigarettes (ECIGs) is increasing, but the impact of ECIG-vapor on cellular processes like inflammation or host defense are less understood. The aim of the present study was to compare the acute effects of traditional cigarettes (TCIGs) and ECIG-exposure on host defense, inflammation, and cellular activation of cell lines and primary differentiated human airway epithelial cells (pHBE). METHODS: We exposed pHBEs and several cell lines to TCIG-smoke or ECIG-vapor. Epithelial host defense and barrier integrity were determined. The transcriptome of airway epithelial cells was compared by gene expression array analysis. Gene interaction networks were constructed and differential gene expression over all groups analyzed. The expression of several candidate genes was validated by qRT-PCR. RESULTS: Bacterial killing, barrier integrity and the expression of antimicrobial peptides were not affected by ECIG-vapor compared to control samples. In contrast, TCIGs negatively affected host defense and reduced barrier integrity in a significant way. Furthermore ECIG-exposure significantly induced IL-8 secretion from Calu-3 cells but had no effect on NCI-H292 or primary cells. The gene expression based on array analysis distinguished TCIG-exposed cells from ECIG and room air-exposed samples. CONCLUSION: The transcriptome patterns of host defense and inflammatory genes are significantly distinct between ECIG-exposed and TCIG-treated cells. The overall effects of ECIGs on epithelial cells are less in comparison to TCIG, and ECIG-vapor does not affect host defense. Nevertheless, although acute exposure to ECIG-vapor induces inflammation, and the expression of S100 proteins, long term in vivo data is needed to evaluate the chronic effects of ECIG use.

11.
Fertil Steril ; 113(5): 970-980.e2, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32222254

RESUMO

OBJECTIVE: To identify differentially abundant miRNAs in sperm samples and spent culture media (SCM) of embryos of different grade toward a prediction of pregnancy outcome. DESIGN: Array-based reverse-transcription quantitative polymerase chain reaction profiling and validation. SETTING: University research institute and in vitro fertilization center. PATIENT(S): Couples (n = 61) undergoing infertility treatment with the use of intracytoplasmic sperm injection. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Abundance levels of miRNAs in combined SCM of embryos of different quality and in sperm samples associated with pregnancy outcome. RESULT(S): Out of 372 screened miRNAs, miR-19b-3p and let-7a-5p were detected consistently in all SCM and sperm samples. The abundance levels of miRNAs were significantly altered between SCM of embryos with different quality (G1, G2, and G3 grades). Specifically, miR-320a and miR-15a-5p were differentially abundant in G1 vs. G2, miR-21-5p in G1 vs. G3, and miR-20a-5p in G2 vs. G3. The abundance levels of combined SCM and sperm derived miRNAs were also significantly altered between different pregnancy outcomes. MiR-19b-3p showed the highest area under the receiver operating characteristic curve values between positive and negative outcomes, with lower abundance levels in both combined SCM and sperm samples associated with a positive pregnancy outcome. MiR-320a, miR-15a-5p, miR-21-5p, and miR-20a-5p showed similar results in combined SCM samples. CONCLUSION(S): miRNA abundance levels in combined SCM and sperm differed significantly depending on embryo quality and pregnancy outcome. MiR-19b-3p may serve as a potential biomarker to predict pregnancy outcome.

12.
JAMA Oncol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134442

RESUMO

Importance: The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures. Objective: To investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants. Design, Setting, and Participants: This multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019. Main Outcomes and Measures: Sensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer. Results: A total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%). Conclusions and Relevance: The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

13.
Lancet Neurol ; 19(5): 462-470, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32059811

RESUMO

Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them.

14.
Int J Immunogenet ; 47(2): 139-148, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32034894

RESUMO

DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.

15.
Int J Immunogenet ; 47(1): 13-23, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31903698

RESUMO

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA-matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two-part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high-throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/métodos , Sistema de Registros , Doadores não Relacionados , Chile , Genética Populacional , Alemanha , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunogenética , Índia , Polônia , Reino Unido , Estados Unidos
16.
Nucleic Acids Res ; 48(D1): D142-D147, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31691816

RESUMO

Since the initial release of miRPathDB, tremendous progress has been made in the field of microRNA (miRNA) research. New miRNA reference databases have emerged, a vast amount of new miRNA candidates has been discovered and the number of experimentally validated target genes has increased considerably. Hence, the demand for a major upgrade of miRPathDB, including extended analysis functionality and intuitive visualizations of query results has emerged. Here, we present the novel release 2.0 of the miRNA Pathway Dictionary Database (miRPathDB) that is freely accessible at https://mpd.bioinf.uni-sb.de/. miRPathDB 2.0 comes with a ten-fold increase of pre-processed data. In total, the updated database provides putative associations between 27 452 (candidate) miRNAs, 28 352 targets and 16 833 pathways for Homo sapiens, as well as interactions of 1978 miRNAs, 24 898 targets and 6511 functional categories for Mus musculus. Additionally, we analyzed publications citing miRPathDB to identify common use-cases and further extensions. Based on this evaluation, we added new functionality for interactive visualizations and down-stream analyses of bulk queries. In summary, the updated version of miRPathDB, with its new custom-tailored features, is one of the most comprehensive and advanced resources for miRNAs and their target pathways.

17.
Environ Sci Technol ; 54(2): 911-920, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31838852

RESUMO

Wastewater treatment plants have been identified as important hubs for small particulate plastic, down to the nanometer scale, from urban areas to the environment. The reuse of sludge as fertilizer in agricultural practices can lead to accumulation of plastic in the soil. In this study, nanoplastic particles and microplastic fibers were synthesized with a passive inorganic tracer to aid in faster and more quantitative analysis using inductively coupled plasma mass spectrometry (ICP-MS). Using the anaerobic digestate of a pilot wastewater treatment plant spiked with metal-doped plastic, the excess sludge was dewatered, ensuring realistic associations between sludge and plastic. The resulting sludge cake was affixed atop an unsaturated porous-medium column of glass beads to assess: (i) the release of particulate plastic from the sludge, and (ii) the accumulation and mobility of plastic and organic matter through the column (analogous to a soil). A total of three particulate plastic treatments were assessed, in triplicate, where the plastic and mobile organic fractions were monitored for 14 pore water volumes. Due to size-limited transport, low deattachment from the sludge and reduced mobility through the column were found for microplastic fibers (>95% retention). However, cotransport between the mobile organic fraction and nanoplastic particles was observed, with 50% of both retained in the column. These results contribute to the understanding of the fate of particulate plastics and to assessing the associated environmental risks of particle mobility and percolation, particularly for nanoplastics.


Assuntos
Plásticos , Esgotos , Microplásticos , Porosidade , Solo , Águas Residuárias
18.
Mol Oncol ; 14(2): 235-247, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31851411

RESUMO

The majority of lung cancer (LC) patients are diagnosed at a late stage, and survival is poor. Circulating RNA molecules are known to have a role in cancer; however, their involvement before diagnosis remains an open question. In this study, we investigated circulating RNA dynamics in prediagnostic LC samples, focusing on smokers, to identify if and when disease-related signals can be detected in serum. We sequenced small RNAs in 542 serum LC samples donated up to 10 years before diagnosis and 519 matched cancer-free controls coming from 905 individuals in the Janus Serum Bank. This sample size provided sufficient statistical power to independently analyze time to diagnosis, stage, and histology. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The greatest number of differentially expressed RNAs was identified around 7 years before diagnosis for early-stage LC and 1-4 years prior to diagnosis for locally advanced and advanced-stage LC, regardless of LC histology. Furthermore, NSCLC and SCLC histologies have distinct prediagnostic signals. The majority of differentially expressed RNAs were associated with cancer-related pathways. The dynamic RNA signals pinpointed different phases of tumor development over time. Stage-specific RNA profiles may be associated with tumor aggressiveness. Our results improve the molecular understanding of carcinogenesis. They indicate substantial opportunity for screening and improved treatment and will guide further research on early detection of LC. However, the dynamic nature of the RNA signals also suggests challenges for prediagnostic biomarker discovery.

19.
Andrologia ; 52(2): e13503, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31876021

RESUMO

MicroRNAs (miRNAs) have recently received a significant amount of attention due to their remarkable influence on post-transcriptional gene regulation. In this study, we aim to provide a catalogue of miRNAs present in spermatozoa, seminal plasma and testicular tissue. Expression profiles of miRNA in spermatozoa and seminal plasma of 16 proven fertile men and testicular tissue of eight men with morphologically and/or histologically confirmed obstructive azoospermia were determined by microarray and RT-qPCR in combination with bioinformatics analyses. A total of 123, 156 and 133 miRNAs were consistently detected in spermatozoa, seminal plasma and testicular tissue respectively. Sixty-four miRNAs were shared across all sample types. Based on miRNAs expression level present in each group, correlation analysis showed moderate-to-strong correlations within the spermatozoa and seminal plasma samples and a wider range of correlations within the testicular tissue samples. The target genes of known miRNAs appeared to be involved in a wide range of biological processes related to reproduction, development and differentiation of germ cells. Our results suggest that there is a certain similarity between spermatozoa and seminal plasma for the relative miRNA expression changes with respect to testicular tissue and provide an overview of the miRNAs present in each sample type.

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