long noncoding RNAs
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Oocyte-to-embryo transition is a process during which an oocyte ovulates, is fertilized, and becomes a developing embryo. It involves the first major genome reprogramming event in life of an organism where gene expression, which gave rise to a differentiated oocyte, is remodeled in order to establish totipotency in blastomeres of an early embryo. This remodeling involves replacement of maternal RNAs with zygotic RNAs through maternal RNA degradation and zygotic genome activation. This review is focused on expression and function of long noncoding RNAs (lncRNAs) and small RNAs during oocyte-to-embryo transition in mammals. LncRNAs are an assorted rapidly evolving collection of RNAs, which have no apparent protein-coding capacity. Their biogenesis is similar to mRNAs including transcriptional control and post-transcriptional processing. Diverse molecular and biological roles were assigned to lncRNAs although most of them probably did not acquire a detectable biological role. Since some lncRNAs serve as precursors for small noncoding regulatory RNAs in RNA silencing pathways, both types of noncoding RNA are reviewed together.
- Klíčová slova
- LTR, RNAi, lncRNA, oocyte, siRNA, zygote,
- MeSH
- blastomery chemie MeSH
- gastrulace MeSH
- lidé MeSH
- malá nekódující RNA genetika MeSH
- RNA dlouhá nekódující genetika MeSH
- savci embryologie genetika MeSH
- stabilita RNA MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- malá nekódující RNA MeSH
- RNA dlouhá nekódující MeSH
We summarize current knowledge regarding regulatory functions of long noncoding RNAs (lncRNAs) in yeast, with emphasis on lncRNAs identified recently in yeast colonies and biofilms. Potential regulatory functions of these lncRNAs in differentiated cells of domesticated colonies adapted to plentiful conditions versus yeast colony biofilms are discussed. We show that specific cell types differ in their complements of lncRNA, that this complement changes over time in differentiating upper cells, and that these lncRNAs target diverse functional categories of genes in different cell subpopulations and specific colony types.
- MeSH
- biofilmy růst a vývoj MeSH
- buněčná diferenciace MeSH
- lidé MeSH
- RNA dlouhá nekódující metabolismus MeSH
- Saccharomyces cerevisiae patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
BACKGROUND/AIM: Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs). MATERIALS AND METHODS: RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers. RESULTS: Our analyses showed that lncRNAs had the strongest predictive potential. The combined set of the best predictors included 14 lncRNAs, and only four PCGs, one circRNA, and no TEs. Epigenetic regulation and recombinational repair were suggested as crucial for AZA response, and network modeling defined three deregulated lncRNAs (CTC-482H14.5, RP11-419K12.2, and RP11-736I24.4) associated with these processes. CONCLUSION: The expression of various ncRNAs can influence the effect of AZA and new ncRNA-based predictive biomarkers can be defined.
- Klíčová slova
- Noncoding RNAs, acute myeloid leukemia, azacytidine, circular RNAs, myelodysplastic syndrome, transposable elements,
- MeSH
- akutní myeloidní leukemie * farmakoterapie genetika MeSH
- azacytidin farmakologie terapeutické užití MeSH
- epigeneze genetická MeSH
- lidé MeSH
- myelodysplastické syndromy * farmakoterapie genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- azacytidin MeSH
- RNA dlouhá nekódující * MeSH
Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single-site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two-phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.
- Klíčová slova
- biomarker, long noncoding RNA, monoclonal gammopathy of undetermined significance, multiple myeloma, qPCR,
- MeSH
- dospělí MeSH
- exozómy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mnohočetný myelom * krev diagnóza mortalita MeSH
- přežití bez známek nemoci MeSH
- RNA dlouhá nekódující krev MeSH
- RNA nádorová krev MeSH
- senioři nad 80 let MeSH
- senioři 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
- klinické zkoušky MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
- RNA nádorová MeSH
In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.
- Klíčová slova
- SR proteins, large intervening non-coding RNA, snRNP, spliceosomes, splicing,
- MeSH
- RNA dlouhá nekódující * genetika MeSH
- sestřih RNA MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
- Klíčová slova
- association study, long noncoding RNA, pancreatic cancer, single nucleotide polymorphism,
- MeSH
- celogenomová asociační studie MeSH
- duktální karcinom slinivky břišní genetika MeSH
- genetická predispozice k nemoci MeSH
- inhibitor p15 cyklin-dependentní kinasy genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádory slinivky břišní genetika MeSH
- RNA dlouhá nekódující genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- výpočetní biologie metody 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
- CDKN2B protein, human MeSH Prohlížeč
- inhibitor p15 cyklin-dependentní kinasy MeSH
- mikro RNA MeSH
- MIRN1256 microRNA, human MeSH Prohlížeč
- RNA dlouhá nekódující MeSH
Meningiomas represent one of the most common types of primary intracranial tumours. However, the specific molecular mechanisms underlying their pathogenesis remain uncertain. Loss of chromosomes 22q, 1p, and 14q have been implicated in most meningiomas. Inactivation of the NF2 gene at 22q12 has been identified as an early event in their pathogenesis, whereas abnormalities of chromosome 14 have been reported in higher-grade as well as recurrent tumours. It has long been supposed that chromosome 14q32 contains a tumour suppressor gene. However, the identity of the potential 14q32 tumour suppressor remained elusive until the Maternally Expressed Gene 3 (MEG3) was recently suggested as an ideal candidate. MEG3 is an imprinted gene located at 14q32 that encodes a non-coding RNA (ncRNA). In meningiomas, loss of MEG3 expression, its genomic DNA deletion and degree of promoter methylation have been found to be associated with aggressive tumour growth. These findings indicate that MEG3 may have a significant role as a novel long noncoding RNA tumour suppressor in meningiomas.
- MeSH
- lidé MeSH
- lidské chromozomy, pár 14 genetika MeSH
- meningeom genetika MeSH
- nádory mozku genetika MeSH
- patologická angiogeneze genetika MeSH
- RNA dlouhá nekódující genetika MeSH
- signální transdukce genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- MEG3 non-coding RNA, human MeSH Prohlížeč
- RNA dlouhá nekódující MeSH
Clear cell renal cell carcinoma (ccRCC) is very common and accounts for most kidney cancer deaths. While many studies are being conducted in finding the prognostic signatures of ccRCC, we believe that ferroptosis, which involves programmed cell death dependent on iron accumulation, has therapeutic potential in ccRCC. Recent research has shown that long noncoding RNAs (lncRNAs) are involved in ferroptosis-related tumour processes and are closely related to survival in patients with ccRCC. Hence, in this study we aim to further explore the role of ferroptosis-related lncRNAs (FRLs) in ccRCC, hoping to establish a signature to predict the survival outcome of ccRCC. We analysed transcriptome data from The Cancer Genome Atlas database (TCGA) and ferroptosis-related genes (FRGs) from FerrDb to identify FRLs using Pearson's correlation. Lasso Cox regression analysis and multivariate Cox proportional hazards models screened seventeen optimal FRLs for developing prognostic signatures. Kaplan-Meier survival curves and ROC curves were then plotted for validating the sensitivity, specificity, and accuracy of the identified signatures. Gene Set Enrichment Analysis and CIBERSORT algorithm were deployed to explore the role of these FRLs in the tumour microenvironment. It was concluded that these models demonstrate excellent performance in predicting prognosis among patients with ccRCC, also indicating association with the clinicopathologic parameters such as tumour grade, tumour stage and tumour immune infiltration. In conclusion, our findings provide novel insights into ferroptosis-related lncRNAs in ccRCC, which are important targets for investigating the tumorigenesis of ccRCC.
- MeSH
- ferroptóza * genetika MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory ledvin * genetika patologie MeSH
- RNA dlouhá nekódující * genetika MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
- RNA dlouhá nekódující * MeSH
- železo MeSH
BACKGROUND: To provide an overview of the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of renal cell carcinoma and their utility as bio-markers for dia-gnosis, prognosis and prediction of treatment response. MATERIALS AND METHODS: A literature search in the Pubmed and Web of Science databases using the keywords variations of “long non-coding RNA” (“lncRNA”, “long noncoding RNA”, “long non-coding RNA”) and “renal cell carcinoma” (“renal cancer”, “renal cell carcinoma”, “kidney cancer”) was performed. The results related to the pathogenesis, dia-gnosis, prognosis and use as therapeutic targets were separated. RESULTS: Long non-coding RNAs regulate gene expression at different levels. They act both as oncogenes and tumor suppressors. The mechanism of their action has not been fully elucidated, but they are actively involved in the regulation of hypoxia inducible factors pathway, epithelial-mesenchymal transition, cell proliferation, cell cycle regulation, apoptosis, local invasion and development of metastases. Aberrant expression in tumor tissue compared to healthy parenchyma and the correlation of expression levels with clinical-pathological features allow the potential use of many lncRNAs as bio-markers for early detection and prognosis of the disease, including the response to targeted therapy. In vitro assays indicate the potential use of lncRNAs as therapeutic targets. CONCLUSION: Our knowledge of long non-coding RNAs in relation to renal cell carcinoma is increasing rapidly. At present, some of them can be considered as promising bio-markers. Further research is needed before they can be introduced into routine clinical practice.
- Klíčová slova
- biomarker, diagnosis, long non-coding RNA, prognosis, renal cell carcinoma,
- MeSH
- buněčný cyklus genetika MeSH
- epitelo-mezenchymální tranzice genetika MeSH
- karcinom z renálních buněk diagnóza genetika mortalita terapie MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin diagnóza genetika mortalita terapie MeSH
- prognóza MeSH
- proliferace buněk genetika MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
- RNA dlouhá nekódující MeSH
Cold and nutrient-activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via the uncoupled respiration and secretion of endocrine factors, thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine-tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive. We identified lncRNAs correlating to interscapular brown adipose tissue (iBAT) function in a high fat diet (HFD) and cold stressed mice. We focused on Gm15551, which has an adipose tissue specific expression profile, is highly upregulated during adipogenesis, and downregulated by β-adrenergic activation in mature adipocytes. Although we performed comprehensive transcriptional and adipocyte physiology profiling in vitro and in vivo, we could not detect an effect of gain or loss of function of Gm15551.
- Klíčová slova
- adipose tissue remodelling, brown adipose tissue, long noncoding RNAs,
- Publikační typ
- časopisecké články MeSH