Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.

• Klíčová slova
• biomarkers, circulating small noncoding RNAs, extracellular vesicles, myelodysplastic syndromes,
• MeSH
• azacytidin farmakologie   MeSH
• biologické markery krev   MeSH
• biologické modely MeSH
• editace RNA genetika   MeSH
• extracelulární vezikuly metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• malá nekódující RNA krev   genetika   MeSH
• mikro RNA genetika   metabolismus   MeSH
• multivariační analýza MeSH
• mutace genetika   MeSH
• myelodysplastické syndromy krev   genetika   patologie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• regulace genové exprese MeSH
• reprodukovatelnost výsledků MeSH
• signální transdukce genetika   MeSH
• výsledek terapie MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azacytidin MeSH
• biologické markery MeSH
• malá nekódující RNA MeSH
• mikro RNA MeSH

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.

• Klíčová slova
• Genetics, Noncoding RNAs, Oncology,
• MeSH
• cirkulující mikroRNA krev   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů diagnóza   MeSH
• mikro RNA krev   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši MeSH
• nádorové biomarkery krev   MeSH
• neuroblastom krev   diagnóza   MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace heterologní MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cirkulující mikroRNA MeSH
• mikro RNA MeSH
• MIRN92 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.

• MeSH
• exozómy genetika   metabolismus   MeSH
• extracelulární vezikuly genetika   metabolismus   MeSH
• kolorektální nádory krev   diagnóza   genetika   metabolismus   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nekódující RNA genetika   metabolismus   MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• nádorové biomarkery MeSH
• nekódující RNA MeSH

Early detection of colorectal cancer (CRC) is the key for prevention and the ability to impact long-term survival of CRC patients. Current CRC screening modalities are inadequate for global application because of low sensitivity and specificity in case of conventional stool-based screening tests, and high costs and a low participation compliance in colonoscopy. An accurate stool- or blood-based screening test with use of innovative biomarkers is an appealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher compliance rates. Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various cancers, including CRC. The discovery that ncRNAs (mainly microRNAs) are stable in stool and in blood plasma and serum presents the opportunity to develop novel strategies taking advantage of circulating ncRNAs as early diagnostic biomarkers of CRC. This chapter is a comprehensive examination of aberrant ncRNAs expression levels in tumor tissue, stool and blood of CRC patients and a summary of the current findings on ncRNAs, including microRNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, circular RNAs and long ncRNAs in regards to their potential usage for screening or early detection of CRC.

• Klíčová slova
• Colorectal cancer, Early diagnosis, Non-coding RNA, Screening, lncRNA, microRNA, piRNAs, snRNAs, snoRNAs,
• MeSH
• adenokarcinom chemie   diagnóza   genetika   MeSH
• adenom chemie   diagnóza   genetika   MeSH
• časná detekce nádoru metody   MeSH
• feces chemie   MeSH
• kolorektální nádory chemie   diagnóza   genetika   MeSH
• krevní plazma MeSH
• lidé MeSH
• nádorové biomarkery analýza   krev   MeSH
• nekódující RNA analýza   krev   MeSH
• pacientův souhlas se zdravotní péčí MeSH
• polypy tlustého střeva chemie   diagnóza   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• senzitivita a specificita MeSH
• sérum MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH
• nekódující RNA MeSH

miRNAs are short noncoding RNAs that post-transcriptionally regulate gene expression. miRNAs' ability to inhibit translation of oncogenes and tumor suppressor genes implies they have an involvement in carcinogenesis. Specific miRNA expression signatures have been identified in a variety of human cancers. More recently, occurrence of miRNAs in the blood serum and plasma of humans has been repeatedly observed. miRNA levels in serum and plasma are more stable, reproducible and consistent among individuals of the same species in comparison with other circulating nucleic acids. Circulating miRNAs have been successfully evaluated in a wide range of solid cancers as promising novel noninvasive biomarkers of early disease onset or relapse. Here we describe the origin of circulating miRNAs, principles of their immense stability and proposed functions, and comprehensively summarize studies focusing on their significance in the most frequently studied cancer types in this regard, including breast, colorectal, lung and prostate cancer.

• MeSH
• kolorektální nádory krev   MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• nádorové biomarkery krev   MeSH
• nádory plic krev   MeSH
• nádory prostaty krev   MeSH
• nádory prsu krev   MeSH
• stabilita RNA MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• nádorové biomarkery MeSH

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
• systematický přehled MeSH
• Názvy látek
• cirkulující mikroRNA * MeSH
• malá nekódující RNA * MeSH
• mikro RNA * MeSH
• nádorové biomarkery MeSH

The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers ?-smooth muscle actin and SM22? was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3'-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway. Keywords: Endothelial progenitor cells, Endothelial to mesenchymal transition, Linc-ROR, MiR-145, Atherosclerosis.

• MeSH
• endotel-mezenchymální transformace MeSH
• endoteliální progenitorové buňky * metabolismus   MeSH
• epitelo-mezenchymální tranzice * MeSH
• kultivované buňky MeSH
• lidé MeSH
• mikro RNA * metabolismus   genetika   MeSH
• pohyb buněk fyziologie   MeSH
• proliferace buněk MeSH
• protein Smad3 * metabolismus   genetika   MeSH
• RNA dlouhá nekódující * genetika   metabolismus   MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Linc-RNA-RoR, human MeSH Prohlížeč
• mikro RNA * MeSH
• MIRN145 microRNA, human MeSH Prohlížeč
• protein Smad3 * MeSH
• RNA dlouhá nekódující * MeSH
• SMAD3 protein, human MeSH Prohlížeč

MicroRNAs (miRNAs) comprise a large group of small noncoding RNAs within a heterogeneous entity of noncoding RNAs, forming potent functional tools regulating the crucial biological processes within cells and the body. Cell-free miRNAs have become one of the novel promising diagnostic, predictive, and prognostic biomarkers for various diseases extensively investigated in recent years. This is due to their presence within extracellular fractions of various body fluids suggesting their potential as noninvasive "liquid biopsy" in case of their dysregulated expression.Among the body fluids, blood plasma and serum along with urine are the most commonly investigated sources of various types of cell-free miRNAs. Another body fluid, i.e., ascites (effusion, peritoneal/pleural fluid) may be the clinically important fluid particularly associated with carcinogenesis in ovarian carcinomas and hepatocellular carcinomas or in case of liver cirrhosis.Here, we provide a protocol for an expression profiling study based on qPCR analyses aimed at finding novel candidate miRNAs via small-scale or large-scale screening and evaluation experiments using liquid biopsies of blood plasma, ascites, and urine. Using this approach may be worth in cases where no (or limited) information is available on miRNA expression in particular diseases and geographic regions, for validation of previously published miRNAs with promising diagnostic potential, particularly in situations where follow-up study is aimed at validating miRNAs coming from (micro) array or NGS experiments, or where funding for large-scale experiments is not available. We demonstrate that assessment of plasma, ascites, and urine miRNAs expression may represent a feasible method to explore the potential for finding novel diagnostic, predictive, and prognostic biomarkers for various diseases.

• Klíčová slova
• Ascites, Biomarker, Cancer, diagnostics, MicroRNA, Plasma, Real-time PCR, Urine,
• MeSH
• ascites MeSH
• biologické markery MeSH
• cirkulující mikroRNA * MeSH
• krevní plazma chemie   MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery MeSH
• následné studie MeSH
• tělesné tekutiny * metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cirkulující mikroRNA * MeSH
• mikro RNA * MeSH
• nádorové biomarkery MeSH

MicroRNAs (miRNAs) are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs) within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.

• MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• myokard imunologie   metabolismus   MeSH
• plíce imunologie   metabolismus   MeSH
• zánět imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH

BACKGROUND: A modern approach to identify biomarkers of solid cancers in tissues and body fluids is based on microRNA (miRNA) expression profiling. miRNAs are a group of approximately 3.000 short noncoding RNAs containing 18-25 nucleotides that regulate gene expression at the post-transcriptional (mRNA) level. The abilities of miRNAs to inhibit the translation or induce degradation of oncogenes and tumor suppressors indicate that they are involved in carcinogenesis. There is increasing evidence that miRNAs regulate apoptosis, cell proliferation, differentiation, and invasion. miRNA expression profiles are therefore often analyzed for molecular diagnostics of solid cancers, similar to analyses based on mRNA profiling. It is important that miRNAs are highly stable and present at high levels in body fluids, including saliva, for analytic usage. miRNAs in saliva have been successfully tested as potential diagnostic biomarkers of many solid cancers. The main advantage of these miRNAs is that saliva samples can be collected non-invasively. AIM: This review aims to summarize current knowledge of circulating miRNAs in solid cancers, with a focus on the use of miRNAs in saliva for oncology diagnostics. Key words: microRNA - saliva - diagnosis - cancer The results of this research have been acquired within CEITEC 2020 (LQ1601) project with fi nancial contribution made by the Ministry of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 3. 2018 Accepted: 15. 5. 2018.

• Klíčová slova
• Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. The authors declare they have no potential confl icts of interest concerning drugs, microRNA - saliva - diagnosis - cancer The results of this research have been acquired within CEITEC 2020 (LQ1601) project with fi nancial contribution made by the Ministry of Education, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 3. 2018 Accepted: 15. 5. 2018, products,
• MeSH
• lidé MeSH
• mikro RNA analýza   MeSH
• nádorové biomarkery analýza   MeSH
• nádory diagnóza   genetika   MeSH
• sliny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• nádorové biomarkery MeSH