The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.

• Klíčová slova
• cancer, delivery systems, long non-coding RNA, microRNA, non-coding RNA, therapy,
• MeSH
• cílená molekulární terapie metody   trendy   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• modely genetické MeSH
• nádory farmakoterapie   genetika   MeSH
• nekódující RNA genetika   MeSH
• protinádorové látky terapeutické užití   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• RNA dlouhá nekódující genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• nekódující RNA MeSH
• protinádorové látky MeSH
• RNA dlouhá nekódující MeSH

A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.

• Klíčová slova
• MALAT1, adenomas, array comparative genomic hybridization, colorectal cancer, long non-coding RNA,
• MeSH
• adenom * genetika   patologie   MeSH
• chromozomální nestabilita MeSH
• kolorektální nádory * genetika   patologie   MeSH
• lidé MeSH
• prekancerózy * genetika   patologie   MeSH
• RNA dlouhá nekódující * genetika   MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MALAT1 long non-coding RNA, human MeSH Prohlížeč
• RNA dlouhá nekódující * MeSH

Multiple myeloma (MM) is a plasma cell malignancy whereby a single clone of plasma cells over-propagates in the bone marrow, resulting in the increased production of monoclonal immunoglobulin. While the complex genetic architecture of MM is well characterized, much less is known about germline variants predisposing to MM. Genome-wide sequencing approaches in MM families have started to identify rare high-penetrance coding risk alleles. In addition, genome-wide association studies have discovered several common low-penetrance risk alleles, which are mainly located in the non-coding genome. Here, we further explored the genetic basis in familial MM within the non-coding genome in whole-genome sequencing data. We prioritized and characterized 150 upstream, 5' untranslated region (UTR) and 3' UTR variants from 14 MM families, including 20 top-scoring variants. These variants confirmed previously implicated biological pathways in MM development. Most importantly, protein network and pathway enrichment analyses also identified 10 genes involved in mitogen-activated protein kinase (MAPK) signaling pathways, which have previously been established as important MM pathways.

• Klíčová slova
• MAPK pathway, familial multiple myeloma, non-coding genome, whole-genome sequencing,
• MeSH
• celogenomová asociační studie * MeSH
• lidé MeSH
• MAP kinasový signální systém MeSH
• mnohočetný myelom * genetika   MeSH
• sekvenování celého genomu MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Multiple myeloma (MM) is the second most common hematooncological disease of malignant plasma cells in the bone marrow. While new treatment brought unprecedented increase of survival of patients, MM pathogenesis is yet to be clarified. Increasing evidence of expression of long non-coding RNA molecules (lncRNA) linked to development and progression of many tumors suggested their important role in tumorigenesis. To date, over 15,000 lncRNA molecules characterized by diversity of function and specificity of cell distribution were identified in the human genome. Due to their involvement in proliferation, apoptosis, metabolism, and differentiation, they have a key role in the biological processes and pathogenesis of many diseases, including MM. This review summarizes current knowledge of non-coding RNAs (ncRNA), especially lncRNAs, and their role in MM pathogenesis. Undeniable involvement of lncRNAs in MM development suggests their potential as biomarkers.

• Klíčová slova
• biomarker, long non-coding RNAs, multiple myeloma,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Non-coding RNAs (ncRNAs) are nucleotide sequences that are known to assume regulatory roles previously thought to be reserved for proteins. Their functions include the regulation of protein activity and localization and the organization of subcellular structures. Sequencing studies have now identified thousands of ncRNAs encoded within the prokaryotic and eukaryotic genomes, leading to advances in several fields including parasitology. ncRNAs play major roles in several aspects of vector-host-pathogen interactions. Arthropod vector ncRNAs are secreted through extracellular vesicles into vertebrate hosts to counteract host defense systems and ensure arthropod survival. Conversely, hosts can use specific ncRNAs as one of several strategies to overcome arthropod vector invasion. In addition, pathogens transmitted through vector saliva into vertebrate hosts also possess ncRNAs thought to contribute to their pathogenicity. Recent studies have addressed ncRNAs in vectors or vertebrate hosts, with relatively few studies investigating the role of ncRNAs derived from pathogens and their involvement in establishing infections, especially in the context of vector-borne diseases. This Review summarizes recent data focusing on pathogen-derived ncRNAs and their role in modulating the cellular responses that favor pathogen survival in the vertebrate host and the arthropod vector, as well as host ncRNAs that interact with vector-borne pathogens.

• Klíčová slova
• Host–pathogen interactions, Non-coding RNAs, Vector-borne infection,
• MeSH
• členovci - vektory MeSH
• eukaryotické buňky MeSH
• infekce přenášené vektorem * MeSH
• interakce hostitele a patogenu genetika   MeSH
• nekódující RNA * genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nekódující RNA * MeSH

The interactions between mitochondria and nucleus substantially influence plant development, stress response and morphological features. The prominent example of a mitochondrial-nuclear interaction is cytoplasmic male sterility (CMS), when plants produce aborted anthers or inviable pollen. The genes responsible for CMS are located in mitochondrial genome, but their expression is controlled by nuclear genes, called fertility restorers. Recent explosion of high-throughput sequencing methods enabled to study transcriptomic alterations in the level of non-coding RNAs under CMS biogenesis. We summarize current knowledge of the role of nucleus encoded regulatory non-coding RNAs (long non-coding RNA, microRNA as well as small interfering RNA) in CMS. We also focus on the emerging data of non-coding RNAs encoded by mitochondrial genome and their possible involvement in mitochondrial-nuclear interactions and CMS development.

• Klíčová slova
• cytoplasmic male sterility, gene expression, global transcriptome, non-coding RNA, pollen development,
• MeSH
• autoinkompatibilita krytosemenných rostlin genetika   MeSH
• Magnoliopsida fyziologie   MeSH
• mitochondriální geny MeSH
• nekódující RNA genetika   metabolismus   MeSH
• neplodnost rostlin genetika   MeSH
• pyl genetika   fyziologie   MeSH
• rostlinné geny MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nekódující RNA MeSH

For the many years, the central dogma of molecular biology has been that RNA functions mainly as an informational intermediate between a DNA sequence and its encoded protein. But one of the great surprises of modern biology was the discovery that protein-coding genes represent less than 2% of the total genome sequence, and subsequently the fact that at least 90% of the human genome is actively transcribed. Thus, the human transcriptome was found to be more complex than a collection of protein-coding genes and their splice variants. Although initially argued to be spurious transcriptional noise or accumulated evolutionary debris arising from the early assembly of genes and/or the insertion of mobile genetic elements, recent evidence suggests that the non-coding RNAs (ncRNAs) may play major biological roles in cellular development, physiology and pathologies. NcRNAs could be grouped into two major classes based on the transcript size; small ncRNAs and long ncRNAs. Each of these classes can be further divided, whereas novel subclasses are still being discovered and characterized. Although, in the last years, small ncRNAs called microRNAs were studied most frequently with more than ten thousand hits at PubMed database, recently, evidence has begun to accumulate describing the molecular mechanisms by which a wide range of novel RNA species function, providing insight into their functional roles in cellular biology and in human disease. In this review, we summarize newly discovered classes of ncRNAs, and highlight their functioning in cancer biology and potential usage as biomarkers or therapeutic targets.

• MeSH
• lidé MeSH
• nádory genetika   MeSH
• nekódující RNA genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nekódující RNA MeSH

BACKGROUND: The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. RESULTS: Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. CONCLUSION: Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs.

• MeSH
• algoritmy MeSH
• bakteriální RNA chemie   genetika   MeSH
• druhová specificita MeSH
• genom bakteriální MeSH
• intergenová DNA MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• nekódující RNA chemie   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• Streptomyces coelicolor genetika   MeSH
• Streptomyces genetika   MeSH
• terminátorové oblasti (genetika) MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH
• Názvy látek
• bakteriální RNA MeSH
• intergenová DNA MeSH
• nekódující RNA MeSH

Cytoplasmic male sterility (CMS) is a widespread phenomenon in flowering plants caused by mitochondrial (mt) genes. CMS genes typically encode novel proteins that interfere with mt functions and can be silenced by nuclear fertility-restorer genes. Although the molecular basis of CMS is well established in a number of crop systems, our understanding of it in natural populations is far more limited. To identify CMS genes in a gynodioecious plant, Silene vulgaris, we constructed mt transcriptomes and compared transcript levels and RNA editing patterns in floral bud tissue from female and hermaphrodite full siblings. The transcriptomes from female and hermaphrodite individuals were very similar overall with respect to variation in levels of transcript abundance across the genome, the extent of RNA editing, and the order in which RNA editing and intron splicing events occurred. We found only a single genomic region that was highly overexpressed and differentially edited in females relative to hermaphrodites. This region is not located near any other transcribed elements and lacks an open-reading frame (ORF) of even moderate size. To our knowledge, this transcript would represent the first non-coding mt RNA associated with CMS in plants and is, therefore, an important target for future functional validation studies.

• Klíčová slova
• Cytoplasmic male sterility, Silene vulgaris, editing, mitochondrion, non-coding RNA, splicing, transcriptome.,
• MeSH
• editace RNA MeSH
• květy genetika   růst a vývoj   MeSH
• mitochondriální geny * MeSH
• nekódující RNA * MeSH
• neplodnost rostlin * MeSH
• rostlinné proteiny genetika   metabolismus   MeSH
• Silene genetika   fyziologie   MeSH
• transkriptom * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• nekódující RNA * MeSH
• rostlinné proteiny MeSH

Over a half of mammalian genomes is occupied by repetitive elements whose ability to provide functional sequences, move into new locations, and recombine underlies the so-called genome plasticity. At the same time, mobile elements exemplify selfish DNA, which is expanding in the genome at the expense of the host. The selfish generosity of mobile genetic elements is in the center of research interest as it offers insights into mechanisms underlying evolution and emergence of new genes. In terms of numbers, with over 20,000 in count, protein-coding genes make an outstanding >2 % minority. This number is exceeded by an ever-growing list of genes producing long non-coding RNAs (lncRNAs), which do not encode for proteins. LncRNAs are a dynamically evolving population of genes. While it is not yet clear what fraction of lncRNAs represents functionally important ones, their features imply that many lncRNAs emerge at random as new non-functional elements whose functionality is acquired through natural selection. Here, we explore the intersection of worlds of mobile genetic elements (particularly retrotransposons) and lncRNAs. In addition to summarizing essential features of mobile elements and lncRNAs, we focus on how retrotransposons contribute to lncRNA evolution, structure, and function in mammals.

• Klíčová slova
• LINE, LTR, MaLR, Retrotransposon, SINE, lncRNA,
• MeSH
• lidé MeSH
• molekulární evoluce MeSH
• myši MeSH
• retroelementy genetika   MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• retroelementy MeSH
• RNA dlouhá nekódující MeSH