microRNA-like RNAs Dotaz Zobrazit nápovědu
Verticillium nonalfalfae (V. nonalfalfae) is one of the most problematic hop (Humulus lupulus L.) pathogens, as the highly virulent fungal pathotypes cause severe annual yield losses due to infections of entire hop fields. In recent years, the RNA interference (RNAi) mechanism has become one of the main areas of focus in plant-fungal pathogen interaction studies and has been implicated as one of the major contributors to fungal pathogenicity. MicroRNA-like RNAs (milRNAs) have been identified in several important plant pathogenic fungi; however, to date, no milRNA has been reported in the V. nonalfalfae species. In the present study, using a high-throughput sequencing approach and extensive bioinformatics analysis, a total of 156 milRNA precursors were identified in the annotated V. nonalfalfae genome, and 27 of these milRNA precursors were selected as true milRNA candidates, with appropriate microRNA hairpin secondary structures. The stem-loop RT-qPCR assay was used for milRNA validation; a total of nine V. nonalfalfae milRNAs were detected, and their expression was confirmed. The milRNA expression patterns, determined by the absolute quantification approach, imply that milRNAs play an important role in the pathogenicity of highly virulent V. nonalfalfae pathotypes. Computational analysis predicted milRNA targets in the V. nonalfalfae genome and in the host hop transcriptome, and the activity of milRNA-mediated RNAi target cleavage was subsequently confirmed for two selected endogenous fungal target gene models using the 5' RLM-RACE approach.
- Klíčová slova
- RNA interference, Verticillium nonalfalfae, fungal pathogen, microRNA-like RNAs, plant-pathogen interactions,
- MeSH
- Ascomycota genetika MeSH
- fungální RNA * MeSH
- fylogeneze MeSH
- genová ontologie MeSH
- interakce hostitele a patogenu MeSH
- konformace nukleové kyseliny MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- malá nekódující RNA genetika MeSH
- mikro RNA genetika MeSH
- nemoci rostlin mikrobiologie MeSH
- regulace genové exprese u hub MeSH
- reprodukovatelnost výsledků MeSH
- stanovení celkové genové exprese MeSH
- výpočetní biologie metody MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fungální RNA * MeSH
- malá nekódující RNA MeSH
- mikro RNA MeSH
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
- Klíčová slova
- RNA modifications, epitranscriptome, lncRNA, tRNA, yeast,
- MeSH
- mikro RNA * genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA * MeSH
- RNA dlouhá nekódující * MeSH
Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically "open" state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.
- MeSH
- buněčné linie MeSH
- embryo savčí * MeSH
- fibroblasty cytologie metabolismus MeSH
- lidé MeSH
- mikro RNA * biosyntéza genetika MeSH
- oktamerní transkripční faktor 3 * biosyntéza genetika MeSH
- regulace genové exprese * MeSH
- techniky buněčného přeprogramování * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mikro RNA * MeSH
- oktamerní transkripční faktor 3 * MeSH
- POU5F1 protein, human MeSH Prohlížeč
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
Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 ℃ for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.
- Klíčová slova
- PC12 cells, dihydropyrimidinase like 3 (Dpysl3), hypothermia, ischaemia, microRNAs,
- MeSH
- buňky PC12 MeSH
- exprese genu MeSH
- hypotermie * genetika MeSH
- ischemie chemicky indukované genetika MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dihydropyrimidinase MeSH Prohlížeč
- Dpysl3 protein, rat MeSH Prohlížeč
- mikro RNA * MeSH
- MIRN326 microRNA, human MeSH Prohlížeč
- MIRN326 microRNA, rat MeSH Prohlížeč
- MIRN497 microRNA, human MeSH Prohlížeč
- MIRN497 microRNA, rat MeSH Prohlížeč
Neuroendocrine prostate cancer (NEPC) represents a variant of prostate cancer that occurs in response to treatment resistance or, to a much lesser extent, de novo. Unravelling the molecular mechanisms behind transdifferentiation of cancer cells to neuroendocrine-like cancer cells is essential for development of new treatment opportunities. This review focuses on summarizing the role of small molecules, predominantly microRNAs, in this phenomenon. A published literature search was performed to identify microRNAs, which are reported and experimentally validated to modulate neuroendocrine markers and/or regulators and to affect the complex neuroendocrine phenotype. Next, available patients' expression datasets were surveyed to identify deregulated microRNAs, and their effect on NEPC and prostate cancer progression is summarized. Finally, possibilities of miRNA detection and quantification in body fluids of prostate cancer patients and their possible use as liquid biopsy in prostate cancer monitoring are discussed. All the addressed clinical and experimental contexts point to an association of NEPC with upregulation of miR-375 and downregulation of miR-34a and miR-19b-3p. Together, this review provides an overview of different roles of non-coding RNAs in the emergence of neuroendocrine prostate cancer.
- Klíčová slova
- exosomes, extracellular vesicles, liquid biomarkers, lncRNA, microRNA, neuroendocrine differentiation/transdifferentiation, patients’ dataset, prostate cancer,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR-145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR-145 in DFs led to the induction of "cellular plasticity" demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency-associated genes including SOX2, KLF4, C-MYC; (c) downregulation of miRNA let-7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR-145 and molecular pathways underlying reprogramming of somatic cells to iPSCs.
- Klíčová slova
- Induced pluripotent stem cells, KLF4, Mesenchymal-to-epithelial transition, OCT4, Reprogramming, SOX2, c-MYC, miR-145, microRNA,
- MeSH
- fibroblasty cytologie metabolismus MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- Krüppel-like faktor 4 MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- molekulární sekvence - údaje MeSH
- přeprogramování buněk * genetika MeSH
- regulace genové exprese MeSH
- reprodukovatelnost výsledků MeSH
- sekvence nukleotidů MeSH
- škára cytologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- KLF4 protein, human MeSH Prohlížeč
- Krüppel-like faktor 4 MeSH
- mikro RNA MeSH
- MIRN145 microRNA, human MeSH Prohlížeč
BACKGROUND: Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of miR-143, miR-145, miR-378 and miR-146a mapped within the 5q deletion. RESULTS: Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, miR-34a was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only miR-378 and miR-146a showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. KLF4, LEF1, SPI1). CONCLUSIONS: The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.
- MeSH
- antigeny CD34 biosyntéza genetika MeSH
- chromozomální delece MeSH
- Krüppel-like faktor 4 MeSH
- lidé MeSH
- lidské chromozomy, pár 5 genetika metabolismus MeSH
- makrocytární anemie genetika metabolismus MeSH
- mikro RNA biosyntéza genetika MeSH
- myelodysplastické syndromy genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD34 MeSH
- KLF4 protein, human MeSH Prohlížeč
- Krüppel-like faktor 4 MeSH
- mikro RNA MeSH
Follistatin-like 1 (FSTL1) is a secreted adipomyokine with a possible link to obesity; however, its connection to extreme obesity currently remains unknown. In order to analyze such association for the very first time, we employed a unique cohort of morbidly and super obese individuals with a mean BMI of 44.77 kg/m2 and measured the levels of circulating FSTL1. We explored the 3' UTR of FSTL1 to locate a genetic variant which impairs microRNA binding. We located and investigated such SNP (rs1057231) in relation to the FSTL1 protein level, obesity status, and other body composition parameters. We observed a significant decline in FSTL1 level in obese subjects in comparison to nonobese ones. The evaluated SNP was found to correlate with FSTL1 only in nonobese subjects. The presented results were not affected by sex since both males and females expressed FSTL1 equally. We suggest that the FSTL1 decrease observed in extremely obese subjects is a result of adipogenesis reduction accompanied by a senescence of preadipocytes which otherwise willingly express FSTL1, increased adipocyte apoptosis, and epigenetic FSTL1 silencing.
- MeSH
- 3' nepřekládaná oblast MeSH
- adipogeneze genetika MeSH
- běloši MeSH
- biologické markery krev MeSH
- dospělí MeSH
- down regulace MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- mladiství MeSH
- morbidní obezita krev genetika MeSH
- obezita krev genetika MeSH
- proteiny související s folistatinem krev genetika MeSH
- senioři MeSH
- vazebná místa MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- 3' nepřekládaná oblast MeSH
- biologické markery MeSH
- FSTL1 protein, human MeSH Prohlížeč
- mikro RNA MeSH
- proteiny související s folistatinem MeSH
Microphthalmia-associated transcription factor (MITF) is a nodal point in melanoma transcriptional network that regulates dozens of genes with critical functions in cell differentiation, proliferation and survival. Highly variable MITF expression levels exist in tumor cell subpopulations conferring marked heterogeneity and plasticity in the tumor tissue. A model has been postulated whereby lower MITF levels favour cell invasion and suppress proliferation, whereas high levels stimulate differentiation and proliferation. Additionally, MITF is considered to be a prosurvival gene and a lineage addiction oncogene in melanoma. Herein, we review how MITF expression may affect the melanoma phenotype with consequences on the survival, invasion and metastasis of melanoma cells, and we discuss the research challenges.
- Klíčová slova
- BRN2, GLI2, SOX2, melanoma, microphthalmia-associated transcription factor,
- MeSH
- apoptóza MeSH
- biologické modely MeSH
- epitelo-mezenchymální tranzice MeSH
- exprese genu MeSH
- faktory domény POU metabolismus MeSH
- homeodoménové proteiny metabolismus MeSH
- invazivní růst nádoru MeSH
- jaderné proteiny metabolismus MeSH
- lidé MeSH
- MAP kinasový signální systém MeSH
- melanom genetika metabolismus patologie MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory kůže genetika metabolismus patologie MeSH
- proliferace buněk MeSH
- protein Gli2 s motivem zinkových prstů MeSH
- RNA nádorová genetika metabolismus MeSH
- stabilita proteinů MeSH
- transkripční faktor spojený s mikroftalmií genetika metabolismus MeSH
- transkripční faktory Krüppel-like metabolismus MeSH
- transkripční faktory SOXB1 metabolismus MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- faktory domény POU MeSH
- GLI2 protein, human MeSH Prohlížeč
- homeodoménové proteiny MeSH
- jaderné proteiny MeSH
- mikro RNA MeSH
- MITF protein, human MeSH Prohlížeč
- protein Gli2 s motivem zinkových prstů MeSH
- RNA nádorová MeSH
- SOX2 protein, human MeSH Prohlížeč
- transcription factor Brn-2 MeSH Prohlížeč
- transkripční faktor spojený s mikroftalmií MeSH
- transkripční faktory Krüppel-like MeSH
- transkripční faktory SOXB1 MeSH