Circular RNA Dotaz Zobrazit nápovědu
In this essay, we aim to draw a short comparison between 2 important research topics - circular and circulating RNAs - and show how they are connected. The findings described here in the field of circular RNAs, which are still quite obscured by the rapidly expanding body of knowledge in biology, have added another dimension to our view of the process of gene expression, which is formed by a more complex network of molecule interactions than we previously thought. The term "circulating RNAs" refers to a broad spectrum of RNA fragments originating from different sources, such as physiologically dying cells, sites of inflammation or cancer cells, and fragments floating in human liquid tissues together with other elements. Fragments of nucleic acids circulating in blood are emerging as promising biomarkers in different medical conditions. Interestingly, circular RNAs have been found to be present in human blood and form a fraction of circulating RNAs. In addition to updating readers on these fast-developing areas of biology, we also stress the need for the study of complex networks of molecule interactions as whole structures (in unison with the thoughts of systems biology), as opposed to the trend toward searching for individual key player molecules. Fundamentally, we want to add to the rationalization and synthesis of new research findings in the scientific literature, because this direction is important not only for students, teachers and researchers, but also for the general population.
- Klíčová slova
- circular RNA, circulating RNA, complex networks, synthesis, systems biology,
- MeSH
- biologické markery MeSH
- kruhová RNA MeSH
- lidé MeSH
- racionalizace MeSH
- RNA genetika MeSH
- systémová biologie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- kruhová RNA MeSH
- RNA MeSH
Lung cancer is one of the main causes of cancer-related death in the world, especially due to its frequency and ineffective therapeutically approaches in the late stages of the disease. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs (circRNAs), a type of RNA with covalently closed continuous loop structures that display high structural resistance and tissue specificity pointed toward a potential biomarker role. Current investigations have identified that circRNAs have a prominent function in the regulation of oncogenic pathways, by regulating gene expression both at transcriptional and post-transcriptional level. The aim of this review is to provide novel information regarding the implications of circRNAs in lung cancer, with an emphasis on the role in disease development and progression. Initially, we explored the potential utility of circRNAs as biomarkers, focusing on function, mechanisms, and correlation with disease progression in lung cancer. Further, we will describe the interaction between circRNAs and other non-coding species of RNA (particularly microRNA) and their biological significance in lung cancer. Describing the nature of these interactions and their therapeutic potential will provide additional insight regarding the altered molecular landscape of lung cancer and consolidate the potential clinical value of these circular transcripts. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.
- Klíčová slova
- biomarkers, circRNAs, lung cancer, therapeutic target,
- MeSH
- cílená molekulární terapie MeSH
- kruhová RNA chemie genetika MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádory plic farmakoterapie genetika metabolismus patologie MeSH
- regulace genové exprese u nádorů * MeSH
- RNA interference MeSH
- signální transdukce MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- nádorové biomarkery * MeSH
BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. MATERIAL AND METHODS: OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by the next generation sequencing (NGS), and OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa-circ-0006203 - hsa-circ-0004872, the primer design and RT-PCR were performed. The expression levels were detected by RT-qPCR. RESULTS: The NGS results demonstrated that circRNAs were abundantly expressed in OSCC, and two circRNAs were significantly differentially expressed. hsa-circ-0006203 - hsa-circ-0004872 were significantly downregulated in OSCC tissue samples and was statistically correlated with pathological differentiation. CONCLUSION: In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, it was our team who firstly explore the regulatory role of the hsa-circ-0006203 - hsa-circ-0004872 network in OSCC. The results indicated that hsa-circ-0006203 - hsa-circ-0004872 may be a potential biomarker for OSCC.
- Klíčová slova
- biomarker, circular RNA, hsa-circ-0004872, hsa-circ-0006203, oral cancer, oral carcinoma,
- MeSH
- biologické markery MeSH
- dlaždicobuněčné karcinomy hlavy a krku MeSH
- kruhová RNA genetika metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory hlavy a krku * genetika MeSH
- nádory úst * genetika MeSH
- RNA genetika metabolismus MeSH
- spinocelulární karcinom * patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- kruhová RNA MeSH
- RNA MeSH
Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher-risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1-mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1-circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR-1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1-circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1-mutated MDS.
- Klíčová slova
- SF3B1, ZEB1, circular RNA, myelodysplastic neoplasms, splicing,
- MeSH
- akutní myeloidní leukemie * MeSH
- fosfoproteiny genetika MeSH
- kruhová RNA genetika MeSH
- lidé MeSH
- mutace genetika MeSH
- myelodysplastické syndromy * genetika MeSH
- sestřihové faktory genetika MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfoproteiny MeSH
- kruhová RNA MeSH
- sestřihové faktory MeSH
- SF3B1 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.
- Klíčová slova
- acute myeloid leukemia, circular RNAs, hematopoiesis, myelodysplastic syndrome,
- MeSH
- akutní myeloidní leukemie krev genetika MeSH
- hematopoéza * MeSH
- kruhová RNA krev genetika MeSH
- lidé MeSH
- myelodysplastické syndromy krev genetika MeSH
- nádorové biomarkery krev genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- nádorové biomarkery MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- Klíčová slova
- biomarker, epigenetic factors, non-coding RNA, osteoarthritis, targeted treatment,
- MeSH
- kruhová RNA MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- osteoartróza * genetika MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- mikro RNA * MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * MeSH
Circular dichroism (CD) is remarkably sensitive to the conformational states of nucleic acids; therefore, CD spectroscopy has been used to study most features of DNA and RNA structures. Quadruplexes are among the significant noncanonical nucleic acids architectures that have received special attentions recently. This article presents examples on the contribution of CD spectroscopy to our knowledge of quadruplex structures and their polymorphism. The examples were selected to demonstrate the potential of this simple method in the quadruplex field. As CD spectroscopy detects only the global feature of a macromolecule, it should preferably be used in combination with other techniques. On the other hand, CD spectroscopy, often as a pioneering approach, can reveal the formation of particular structural arrangements, to search for the conditions stabilizing the structures, to follow the transitions between various structural states, to explore kinetics of their appearance, to determine thermodynamic parameters and also detect formation of higher order structures. This article aims to show that CD spectroscopy is an important complementary technique to NMR spectroscopy and X-ray diffraction in quadruplex studies.
- MeSH
- cirkulární dichroismus metody MeSH
- difrakce rentgenového záření MeSH
- DNA chemie MeSH
- G-kvadruplexy * MeSH
- guanin chemie MeSH
- kinetika MeSH
- konformace nukleové kyseliny * MeSH
- oligonukleotidy chemie MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
- guanin MeSH
- oligonukleotidy MeSH
Here we review studies that provided important information about conformational properties of DNA using circular dichroic (CD) spectroscopy. The conformational properties include the B-family of structures, A-form, Z-form, guanine quadruplexes, cytosine quadruplexes, triplexes and other less characterized structures. CD spectroscopy is extremely sensitive and relatively inexpensive. This fast and simple method can be used at low- as well as high-DNA concentrations and with short- as well as long-DNA molecules. The samples can easily be titrated with various agents to cause conformational isomerizations of DNA. The course of detected CD spectral changes makes possible to distinguish between gradual changes within a single DNA conformation and cooperative isomerizations between discrete structural states. It enables measuring kinetics of the appearance of particular conformers and determination of their thermodynamic parameters. In careful hands, CD spectroscopy is a valuable tool for mapping conformational properties of particular DNA molecules. Due to its numerous advantages, CD spectroscopy significantly participated in all basic conformational findings on DNA.
- MeSH
- A-DNA chemie MeSH
- cirkulární dichroismus * MeSH
- denaturace nukleových kyselin MeSH
- DNA chemie MeSH
- G-kvadruplexy MeSH
- konformace nukleové kyseliny MeSH
- Z-DNA chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- A-DNA MeSH
- DNA MeSH
- triplex DNA MeSH Prohlížeč
- Z-DNA MeSH
Nucleic acids bear the genetic information and participate in its expression and evolution during replication, repair, recombination, transcription, and translation. These phenomena are mostly based on recognition of nucleic acids by proteins. The major factor enabling the specific recognition is structure. Circular dichroism (CD) spectroscopy is very useful to study secondary structures of nucleic acids, in general, and DNA, in particular. CD sensitively reflects isomerizations among distinct conformational states. The isomerizations may operate as molecular switches regulating various physiological or pathological processes. Here, we review CD spectra of nucleic acids, beginning with early studies on natural DNA molecules through analyses of synthetic polynucleotides to study of selected genomic fragments.
- MeSH
- cirkulární dichroismus * MeSH
- DNA chemie genetika MeSH
- G-kvadruplexy * MeSH
- lidé MeSH
- sekvence nukleotidů MeSH
- trinukleotidové repetice MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on blood-derived fluids, other biofluids may be more informative. We present an atlas of messenger, circular, and small RNA transcriptomes of a comprehensive collection of 20 human biofluids. By means of synthetic spike-in controls, we compare RNA content across biofluids, revealing a 10,000-fold difference in concentration. The circular RNA fraction is increased in most biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. Our atlas enables an informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Spike-normalized data are publicly available in the R2 web portal for further exploration.
- Klíčová slova
- RNA sequencing, biofluids, biomarker, cell-free RNA, circular RNA, extracellular RNA, liquid biopsy, messenger RNA, small RNA,
- MeSH
- biologické markery * MeSH
- kohortové studie MeSH
- lidé MeSH
- RNA genetika metabolismus MeSH
- sekvenční analýza RNA metody MeSH
- stanovení celkové genové exprese metody MeSH
- tělesné tekutiny metabolismus MeSH
- transkriptom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- biologické markery * MeSH
- RNA MeSH