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

Systems biology approaches, especially in the big data era, have revolutionized modern parasitology. Of the many different molecules participating in parasite-host interactions, noncoding RNAs (ncRNAs) are now known to be (i) transmitted by the vector to possibly modulate vertebrate host responses and favor vector survival and (ii) regulated in the host by parasites to favor parasite survival. Here we provide an overview of the involvement of ncRNAs in the parasite-vector-host triad and their effect on host homeostasis based on recent advances and accumulating knowledge about the role of endogenous vertebrate noncoding RNAs in vertebrate host physiology.

• Klíčová slova
• arthropod vectors, epigenetics, miRNA, noncoding RNA, parasite–vertebrate–host interaction, pathogenesis,
• MeSH
• homeostáza fyziologie   MeSH
• infekce přenášené vektorem * MeSH
• interakce hostitele a parazita genetika   imunologie   MeSH
• lidé MeSH
• nekódující RNA genetika   imunologie   MeSH
• obratlovci imunologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nekódující RNA MeSH

The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex terminates transcription of noncoding RNA genes and promotes exosome-dependent processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation. NNS-dependent termination and degradation are coupled, but the mechanism underlying this coupling remains enigmatic. Here we provide structural and functional evidence demonstrating that the same domain of Nrd1p interacts with RNA polymerase II and Trf4p in a mutually exclusive manner, thus defining two alternative forms of the NNS complex, one involved in termination and the other in degradation. We show that the Nrd1-Trf4 interaction is required for optimal exosome activity in vivo and for the stimulation of polyadenylation of NNS targets by TRAMP in vitro. We propose that transcription termination and RNA degradation are coordinated by switching between two alternative partners of the NNS complex.

• MeSH
• DNA-dependentní DNA-polymerasy chemie   metabolismus   MeSH
• exozómy metabolismus   MeSH
• fungální RNA metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární modely MeSH
• nekódující RNA metabolismus   MeSH
• polyadenylace MeSH
• proteiny vázající RNA chemie   metabolismus   MeSH
• RNA-polymerasa II metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny chemie   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   MeSH
• stabilita RNA MeSH
• terminace genetické transkripce * MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA-dependentní DNA-polymerasy MeSH
• fungální RNA MeSH
• nekódující RNA MeSH
• NRD1 protein, S cerevisiae MeSH Prohlížeč
• PAP2 protein, S cerevisiae MeSH Prohlížeč
• proteiny vázající RNA MeSH
• RNA-polymerasa II MeSH
• Saccharomyces cerevisiae - proteiny MeSH

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

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

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic. METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients. RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients. CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.

• Klíčová slova
• Aneuploidy, MSS, Noncoding RNA, Tumorigenesis,
• MeSH
• Aurora kinasa B metabolismus   MeSH
• azoxymethan toxicita   MeSH
• chemorezistence genetika   MeSH
• chromozomální nestabilita * MeSH
• cytogenetické vyšetření MeSH
• dextrany toxicita   MeSH
• experimentální nádory chemicky indukované   genetika   patologie   MeSH
• genový knockdown MeSH
• karcinogeneze genetika   MeSH
• kolon cytologie   patologie   MeSH
• kolorektální nádory chemicky indukované   genetika   patologie   MeSH
• lidé MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• organoidy MeSH
• primární buněčná kultura MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• signální transdukce genetika   MeSH
• střevní sliznice cytologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• AURKB protein, human MeSH Prohlížeč
• Aurora kinasa B MeSH
• azoxymethan MeSH
• BOP1 protein, human MeSH Prohlížeč
• dextrany MeSH
• long non-coding RNA CCAT2, human MeSH Prohlížeč
• MYC protein, human MeSH Prohlížeč
• proteiny vázající RNA MeSH
• protoonkogenní proteiny c-myc MeSH
• 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

Most biochemical, computational and genetic approaches to gene finding assume the Central Dogma and look for genes that make mRNA and have ORFs. These approaches essentially do not work for one class of genes--the noncoding RNA. In all living organisms RNA is involved in a number of essential cell processes. Functional analysis of genome sequences has largely ignored RNA genes and their structures. Different RNA species including rRNA, tRNA, mRNA and sRNA (small RNA) are important structural, transfer, informational, and regulatory molecules containing complex folded conformations that participate in recognition and catalytic processes. Noncoding RNAs play an number of important structural, catalytic and regulatory roles in the cell. The size of the sRNA genes ranges from 70 to 500 nucleotides. Several transcripts of these genes are processed by RNAases and their final products are smaller. The encoding genes are localized between two ORFs and do not overlap with ORFs on the complementary DNA strand. As aptamers, some sRNA bind small molecular components (metal ions, peptides and nucleotides). This review summarizes recent data on the functions of prokaryotic sRNAs and approaches to their identification.

• MeSH
• Bacteria genetika   MeSH
• bakteriální RNA * chemie   genetika   metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• nekódující RNA * chemie   genetika   metabolismus   MeSH
• prokaryotické buňky metabolismus   MeSH
• sekvence nukleotidů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• bakteriální RNA * MeSH
• nekódující RNA * MeSH

Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.

• Klíčová slova
• gene expression regulation, miRNA lncRNA., non-coding RNA,
• MeSH
• lidé MeSH
• mikro RNA genetika   fyziologie   MeSH
• nekódující RNA genetika   fyziologie   MeSH
• regulace genové exprese genetika   fyziologie   MeSH
• RNA dlouhá nekódující genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• nekódující RNA MeSH
• 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