Identifying patients likely to develop breast cancer recurrence remains a challenge. Thus, the discovery of biomarkers capable of diagnosing recurrence is of the utmost importance. MiRNAs are small, non-coding RNA molecules which are known to regulate genetic expression and have previously demonstrated relevance as biomarkers in malignancy. To perform a systematic review evaluating the role of miRNAs in predicting breast cancer recurrence. A formal systematic search of PubMed, Scopus, Web of Science, and Cochrane databases was performed. This search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist. A total of 19 studies involving 2287 patients were included. These studies identified 44 miRNAs which predicted breast cancer recurrence. Results from nine studies assessed miRNAs in tumour tissues (47.4%), eight studies included circulating miRNAs (42.1%), and two studies assessed both tumour and circulating miRNAs (10.5%). Increased expression of 25 miRNAs were identified in patients who developed recurrence, and decreased expression of 14 miRNAs. Interestingly, five miRNAs (miR-17-5p, miR-93-5p, miR-130a-3p, miR-155, and miR-375) had discordant expression levels, with previous studies indicating both increased and reduced expression levels of these biomarkers predicting recurrence. MiRNA expression patterns have the ability to predict breast cancer recurrence. These findings may be used in future translational research studies to identify patients with breast cancer recurrence to improve oncological and survival outcomes for our prospective patients.

• Klíčová slova
• breast cancer, microRNAs, oncological outcomes, recurrence, survival outcomes,
• MeSH
• cirkulující mikroRNA * MeSH
• lidé MeSH
• malá nekódující RNA * MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádorové biomarkery genetika   MeSH
• nádory prsu * diagnóza   genetika   metabolismus   MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• cirkulující mikroRNA * MeSH
• malá nekódující RNA * MeSH
• mikro RNA * MeSH
• nádorové biomarkery MeSH

MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the post-transcriptional regulation of biological processes. miRNAs regulate transcripts through direct binding involving the Argonaute protein family. The exact rules of binding are not known, and several in silico miRNA target prediction methods have been developed to date. Deep learning has recently revolutionized miRNA target prediction. However, the higher predictive power comes with a decreased ability to interpret increasingly complex models. Here, we present a novel interpretation technique, called attribution sequence alignment, for miRNA target site prediction models that can interpret such deep learning models on a two-dimensional representation of miRNA and putative target sequence. Our method produces a human readable visual representation of miRNA:target interactions and can be used as a proxy for the further interpretation of biological concepts learned by the neural network. We demonstrate applications of this method in the clustering of experimental data into binding classes, as well as using the method to narrow down predicted miRNA binding sites on long transcript sequences. Importantly, the presented method works with any neural network model trained on a two-dimensional representation of interactions and can be easily extended to further domains such as protein-protein interactions.

• Klíčová slova
• CLASH, deep learning, interpretation, miRNA target prediction, visualization,
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR. RESULTS: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006). CONCLUSION: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.

• Klíčová slova
• Colorectal cancer, cetuximab, chemotherapy, let-7c, miR-125b, miR-17, microRNA, panitumumab,
• MeSH
• cetuximab farmakologie   terapeutické užití   MeSH
• chemorezistence genetika   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• down regulace MeSH
• erbB receptory antagonisté a inhibitory   genetika   MeSH
• inhibitory proteinkinas farmakologie   terapeutické užití   MeSH
• kolorektální nádory farmakoterapie   genetika   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• panitumumab farmakologie   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cetuximab MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• inhibitory proteinkinas MeSH
• mikro RNA MeSH
• MIRN125 microRNA, human MeSH Prohlížeč
• MIRN17 microRNA, human MeSH Prohlížeč
• mirnlet7 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• panitumumab MeSH

Genetic variations in miRNAs binding site might participate in cancer risk. This study aimed to systematically review the association between miRNA-binding site polymorphisms and colorectal cancer (CRC). Electronic literature search was carried out on PubMed, Web of Science (WOS), Scopus, and Embase. All types of observational studies till 30 November 2018 were included. Overall 85 studies (21 SNPs) from two systematic searches were included analysis. The results showed that in the Middle East population, the minor allele of rs731236 was associated with decreased risk of CRC (heterozygote model: 0.76 [0.61-0.95]). The minor allele of rs3025039 was related to increased risk of CRC in East Asian population (allelic model: 1.25 [1.01-1.54]). Results for rs3212986 were significant in overall and subgroup analysis (P < .05). For rs1801157 in subgroup analysis the association was significant in Asian populations (including allelic model: 2.28 [1.11-4.69]). For rs712, subgroup analysis revealed a significant (allelic model: 1.41 [1.23-1.61]) and borderline (allelic model: 0.92 [0.84-1.00]) association in Chinese and Czech populations, respectively. The minor allele of rs17281995 increased risk of CRC in different genetic models (P < .05). Finally, rs5275, rs4648298, and rs61764370 did not show significant associations. In conclusion, minor allele of rs3025039, rs3212986, and rs712 polymorphisms increases the risk of CRC in the East Asian population, and heterozygote model of rs731236 polymorphism shows protective effect in the Middle East population. In Europeans, the minor allele of rs17281995 may increase the risk of CRC, while rs712 may have a protective effect. Further analysis based on population stratifications should be considered in future studies.

• Klíčová slova
• colorectal cancer, meta-analysis, microRNAs, polymorphism,
• MeSH
• 3' nepřekládaná oblast genetika   MeSH
• alely MeSH
• Asijci genetika   MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory epidemiologie   genetika   MeSH
• lidé MeSH
• mikro RNA metabolismus   MeSH
• pozorovací studie jako téma MeSH
• regulace genové exprese u nádorů MeSH
• rizikové faktory MeSH
• vazebná místa genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Dálný východ epidemiologie   MeSH
• Střední východ epidemiologie   MeSH
• Názvy látek
• 3' nepřekládaná oblast MeSH
• mikro RNA MeSH

Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs) is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method), pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration) and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.

• Klíčová slova
• animal model, colorectal cancer, gallbladder cancer, gastric cancer, mice, microRNA, pancreatic cancer, preclinical testing,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The most important reason for therapy failure in pediatric acute myeloid leukemia (AML) is relapse. In order to identify miRNAs that contribute to the clonal evolution towards relapse in pediatric AML, miRNA expression profiling of 127 de novo pediatric AML cases were used. In the diagnostic phase, no miRNA signatures could be identified that were predictive for relapse occurrence, in a large pediatric cohort, nor in a nested mixed lineage leukemia (MLL)-rearranged pediatric cohort. AML with MLL- rearrangements are found in 15-20% of all pediatric AML samples, and reveal a relapse rate up to 50% for certain translocation partner subgroups. Therefore, microRNA expression profiling of six paired initial diagnosis-relapse MLL-rearranged pediatric AML samples (test cohort) and additional eight paired initial diagnosis-relapse samples with MLL-rearrangements (validation cohort) was performed. A list of 53 differentially expressed miRNAs was identified of which the miR-106b~25 cluster, located in intron 13 of MCM7, was the most prominent. These differentially expressed miRNAs however could not predict a relapse in de novo AML samples with MLL-rearrangements at diagnosis. Furthermore, higher mRNA expression of both MCM7 and its upstream regulator E2F1 was found in relapse samples with MLL-rearrangements. In conclusion, we identified the miR-106b~25 cluster to be upregulated in relapse pediatric AML with MLL-rearrangements.

• Klíčová slova
• MLL, acute myeloid leukemia, miR-106b~25, relapse,
• MeSH
• akutní myeloidní leukemie genetika   patologie   MeSH
• dítě MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• introny genetika   MeSH
• karcinogeneze genetika   MeSH
• klonální evoluce MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   patologie   MeSH
• MCM komplex, komponenta 7 metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• mikro RNA genetika   MeSH
• mladiství MeSH
• multigenová rodina MeSH
• předškolní dítě MeSH
• protoonkogenní protein MLL genetika   MeSH
• regulace genové exprese u leukemie * MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktor E2F1 metabolismus   MeSH
• translokace genetická MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• E2F1 protein, human MeSH Prohlížeč
• histonlysin-N-methyltransferasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• MCM komplex, komponenta 7 MeSH
• MCM7 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• mikro RNA MeSH
• MIRN106 microRNA, human MeSH Prohlížeč
• protoonkogenní protein MLL MeSH
• transkripční faktor E2F1 MeSH

Serum microRNAs are emerging as a clinically useful tool for early and non-invasive detection of various cancer types including renal cell carcinoma (RCC). Based on our previous results, we performed the study to analyze circulating serum miR-378 and miR-210 in patients with various histological subtypes of RCC. RNA was purified from blood serum samples of 195 RCC patients and 100 healthy controls. The levels of miR-378 and miR-210 in serum were determined absolutely using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs were compared in 20 RCC patients. Significantly increased serum levels of both miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy controls with 80% sensitivity and 78% specificity if analyzed in combination (p<0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p<0.0001). Increased level of miR-378 positively correlates with disease-free survival (p=0.036) and clinical stage (p=0.0476). The analysis of serum miR-378 and miR-210 proved their potential to serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.

• Klíčová slova
• biomarker, blood serum, microRNA, renal cell carcinoma,
• MeSH
• karcinom z renálních buněk krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• nádorové biomarkery krev   MeSH
• nádory ledvin krev   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN210 microRNA, human MeSH Prohlížeč
• MIRN378 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

BACKGROUND: Screening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups. METHODS: The expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues. RESULTS: High levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed. CONCLUSION: We identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups.

• MeSH
• adenom krev   patologie   MeSH
• časná detekce nádoru MeSH
• diferenciální diagnóza * MeSH
• kolorektální nádory krev   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• polypy tlustého střeva krev   patologie   MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN150 microRNA, human MeSH Prohlížeč
• MIRN34 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

BACKGROUND: There is no standard serum biomarker used for diagnosis or early detection of recurrence for renal cell carcinoma (RCC) patients. MicroRNAs (miRNAs) are abundant and highly stable in blood serum, and have been recently described as powerful circulating biomarkers in a wide range of solid cancers. Our aim was to identify miRNA signature that can distinguish the blood serum of RCC patients and matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. METHODS: In the screening phase of the study, blood serum of 15 RCC patients and 12 matched healthy controls were analyzed by use of the TaqMan Low-Density Arrays enabling parallel identification of expression levels of 667 miRNAs through qRT-PCR-based approach. In the validation phase, identified miRNAs were further evaluated on the independent group of 90 RCC patients and 35 matched healthy controls by use of individual qRT-PCR assays and statistically evaluated. RESULTS: We identified 30 miRNAs differentially expressed between serum of RCC patients and healthy controls: 19 miRNAs were up-regulated and 11 miRNAs were down-regulated in RCC patients. MiR-378, miR-451 and miR-150 were further evaluated in the independent group of patients, and two of them were successfully validated: levels of miR-378 were increased (p = 0.0003, AUC = 0.71), miR-451 levels were decreased (p < 0.0001, AUC = 0.77) in serum of RCC patients. Combination of miR-378 and miR-451 enable identification of RCC serum with the sensitivity of 81%, specificity 83% and AUC = 0.86. CONCLUSIONS: Circulating miRNAs in serum are promising biomarkers in RCC.

• MeSH
• dospělí MeSH
• karcinom z renálních buněk krev   diagnóza   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory ledvin krev   diagnóza   genetika   MeSH
• plošný screening MeSH
• regulace genové exprese u nádorů MeSH
• reprodukovatelnost výsledků MeSH
• ROC křivka MeSH
• senioři MeSH
• shluková analýza MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN378 microRNA, human MeSH Prohlížeč
• MIRN451 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery.

• MeSH
• DNA modifikační methylasy genetika   metabolismus   MeSH
• dospělí MeSH
• enzymy opravy DNA genetika   metabolismus   MeSH
• glioblastom diagnóza   genetika   metabolismus   mortalita   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• mikro RNA biosyntéza   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• nádory mozku diagnóza   genetika   metabolismus   mortalita   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• promotorové oblasti (genetika) * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA modifikační methylasy MeSH
• enzymy opravy DNA MeSH
• MGMT protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIrn181 microRNA, human MeSH Prohlížeč
• MIRN195 microRNA, human MeSH Prohlížeč
• MIRN196 microRNA, human MeSH Prohlížeč
• MIRN21 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• nádorové supresorové proteiny MeSH