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Utility Of Plasma circBNC2 As A Diagnostic Biomarker In Epithelial Ovarian Cancer

ONCOTARGETS AND THERAPY 2019年 12卷 9715-9723页

作者： Hu, Yingchao Zhu, Yapei Zhang, Wen Lang, Jinghe Ning, Li Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Obstet & Gynecol Beijing 100730 Peoples R China Peking Union Med Coll Beijing 100730 Peoples R China Chinese Acad Med Sci Canc Hosp Dept Gynecol Oncol Natl Canc Ctr Beijing 100021 Peoples R China Peking Union Med Coll Beijing 100021 Peoples R China

Background: Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in women. Due to a lacking of early detection method, its five-year survival rate is only 30%. Nevertheless, novel biomarkers for diagnosis remain to be discovered. The potential of microrna signatures in the diagnosis of EOC has been especially described in recent years. In our previous experiments, we identified that circBNC2 was downregulated in EOC specimens, and was associated with advanced tumor stage and lymph node metastasis (LNM) by performing circrna-sequencing analysis. The aim of this study was to explore the diagnostic value of circBNC2 in patients with epithelial ovarian cancer (EOC). Methods: Plasma from 249 age and menopause-matched women (83 with EOC;83 with benign ovarian cyst;83 were healthy volunteers) was collected prior to surgery. CircBNC2 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were analyzed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. Results: CircBNC2 was downregulated in EOC and had higher ROC AUC in comparing EOC to benign (ROC AUC 0.879, sensitivity 96.4%, specificity 80.7%) or healthy (ROC AUC 0.923, sensitivity 95.2%, specificity 85.5%) cohorts than HE4 (ROC AUC: 0.742, benign cohort;0.779, healthy cohort) and CA125 (ROC AUC: 0.373, benign cohort;0.713, healthy cohort). Early stage EOC vs benign (ROC AUC 0.864, sensitivity 92.0%, specificity 80.7%) and healthy (ROC AUC 0.908, sensitivity 92.0%, specificity 85.5%) cohorts could be significantly separated by circBNC2. CircBNC2 performed alike in pre- and postmenopausal women, within EOC compared to the benign or healthy cohort. Conclusion: CircBNC2 is downregulated in EOC (both in tissue and plasma samples) and might present promising novel biomarker for EOC. Further studies

关键词： epithelial ovarian cancer circular rna noncoding rna diagnosis biomarker

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Micrornas in diabetic nephropathy: functions, biomarkers, and therapeutic targets

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YEAR IN DIABETES AND OBESITY 2015年第1期1353卷 72-88页

作者： Kato, Mitsuo Natarajan, Rama City Hope Natl Med Ctr Beckman Res Inst Dept Diabet Complicat Duarte CA 91010 USA

Micrornas (mirnas) are short noncoding rnas that regulate gene expression by posttranscriptional and epigenetic mechanisms and thereby affect many cellular processes and disease states. Over 2,000 human mature mirnas have been identified, and at least 60% of all human protein-coding genes are known to be regulated by mirnas. Microrna biogenesis involves classical transcription regulation and processing by key ribonucleases, as well as other protein factors and epigenetic mechanisms. Diabetic nephropathy (DN), a severe microvascular complication frequently associated with diabetes mellitus, is a major cause of renal failure. Although several mechanisms of regulation of key renal genes implicated in DN pathogenesis have been identified, a greater understanding is needed to develop better treatment modalities. Recent studies show that mirnas induced in renal cells in vivo and in vitro under diabetic conditions can promote the accumulation of extracellular matrix proteins related to fibrosis and glomerular dysfunction. In this review, we highlight the significance of the expression of mirnas in various stages of DN and emerging approaches to exploit them as biomarkers for early detection or novel therapeutic targets to prevent progression of DN.

关键词： micrornas diabetic nephropathy transforming growth factor beta 1 signal transduction biomarkers therapeutics noncoding rna

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How eukaryotic genes are transcribed

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CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY 2009年第2-3期44卷 117-141页

作者： Venters, Bryan J. Pugh, B. Franklin Penn State Univ Ctr Eukaryot Gene Regulat Dept Biochem & Mol Biol University Pk PA 16802 USA

Regulation of eukaryotic gene expression is far more complex than one might have imagined 30 years ago. However, progress towards understanding gene regulatory mechanisms has been rapid and comprehensive, which has made the integration of detailed observations into broadly connected concepts a challenge. This review attempts to integrate the following concepts: (1) a well-defined organization of nucleosomes and modification states at most genes;(2) regulatory networks of sequence-specific transcription factors;(3) chromatin remodeling coupled to promoter assembly of the general transcription factors and rna polymerase 11;and (4) phosphorylation states of rna polymerase 11 coupled to chromatin modification states during transcription. The wealth of new insights arising from the tools of biochemistry, genomics, cell biology, and genetics is providing a remarkable view into the mechanics of gene regulation.

关键词： Gene regulation chromatin genome-wide pre-initiation complex histone modification transcription cycle noncoding rna

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Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2005年第15期102卷 5495-5500页

作者： Tupy, JL Bailey, AM Dailey, G Evans-Holm, M Siebel, CW Misra, S Celniker, SE Rubin, GM Univ Calif Berkeley Lawrence Berkeley Natl Lab Berkeley Drosophila Genome Project Berkeley CA 94720 USA Univ Calif Berkeley Lawrence Berkeley Natl Lab Dept Genome Sci Berkeley CA 94720 USA Univ Calif Berkeley Dept Mol & Cell Biol Berkeley CA 94720 USA Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA

Analysis of EST and cDNA collections from a number of metazoan species has identified genes encoding long polyadenylated transcripts that do not contain ORFs of lengths typical for protein-encoding mrnas. noncoding functions of such polyadenylated transcripts have been elucidated in only a few examples. The corresponding genes neither contain hallmark sequence motifs nor appear to have been conserved across phyla. Thus, it is impossible to systematically identify new members of this class of gene by using sequence homology and traditional gene-finding algorithms that depend on protein-coding potential. Consequently, even their approximate number has not been established for any metazoan genome. We curated polyadenylated transcripts with limited protein-coding capacity from intergenic regions of the Drosophila melanogaster genome. We used RT-PCR assays, hybridization to rna blots and whole-mount embryos, and computational analyses to characterize candidate transcripts. We verify the structures and expression of 17 distinct, likely non-protein-coding polyadenylated transcripts. We show that the expression of many of these transcripts is conserved in other Drosophila species, indicating that they have important biological functions.

关键词： genome noncoding rna noncoding rna Drosophila pseudoobscura Drosophila virilis

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Regulation by 3′-Untranslated Regions

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ANNUAL REVIEW OF GENETICS, VOL 51 2017年第1期51卷 171-194页

作者： Mayr, Christine Mem Sloan Kettering Canc Ctr Dept Canc Biol & Genet New York NY 10065 USA

3'-untranslated regions (3'-UTRs) are the noncoding parts of mrnas. Compared to yeast, in humans, median 3'-UTR length has expanded approximately tenfold alongside an increased generation of alternative 3'-UTR isoforms. In contrast, the number of coding genes, as well as coding region length, has remained similar. This suggests an important role for 3'-UTRs in the biology of higher organisms. 3'-UTRs are best known to regulate diverse fates of mrnas, including degradation, translation, and localization, but they can also function like long noncoding or small rnas, as has been shown for whole 3'-UTRs as well as for cleaved fragments. Furthermore, 3'-UTRs determine the fate of proteins through the regulation of protein-protein interactions. They facilitate cotranslational protein complex formation, which establishes a role for 3'-UTRs as evolved eukaryotic operons. Whereas bacterial operons promote the interaction of two subunits, 3'-UTRs enable the formation of protein complexes with diverse compositions. All of these 3'-UTR functions are accomplished by effector proteins that are recruited by rna-binding proteins that bind to 3'-UTR cis-elements. In summary, 3'-UTRs seem to be major players in gene regulation that enable local functions, compartmentalization, and cooperativity, which makes them important tools for the regulation of phenotypic diversity of higher organisms.

关键词： noncoding rna regulatory rna alternative 3 '-UTRs alternative polyadenylation cotranslational protein complex formation cellular organization mrna localization rna-binding proteins cooperativity accessibility of regulatory elements

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Next-generation technologies and data analytical approaches for epigenomics

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ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2014年第3期55卷 155-170页

作者： Mensaert, Klaas Denil, Simon Trooskens, Geert Van Criekinge, Wim Thas, Olivier De Meyer, Tim Univ Ghent Fac Biosci Engn Dept Math Modelling Stat & Bioinformat B-9000 Ghent Belgium Univ Wollongong Sch Math & Appl Stat NIASRA Wollongong NSW 2522 Australia

Epigenetics refers to the collection of heritable features that modulate the genome-environment interaction without being encoded in the actual DNA sequence. While being mitotically and sometimes even meiotically transmitted, epigenetic traits often demonstrate extensive flexibility. This allows cells to acquire diverse gene expression patterns during differentiation, but also to adapt to a changing environment. However, epigenetic alterations are not always beneficial to the organism, as they are, for example, frequently identified in human diseases such as cancer. Accurate and cost-efficient genome-scale profiling of epigenetic features is thus of major importance to pinpoint these "epimutations," for example, to monitor the epigenetic impact of environmental exposure. Over the last decade, the field of epigenetics has been revolutionized by several innovative "epigenomics" technologies exactly addressing this need. In this review, we discuss and compare widely used next-generation methods to assess DNA methylation and hydroxymethylation, noncoding rna expression, histone modifications, and nucleosome positioning. Although recent methods are typically based on "second-generation" sequencing, we also pay attention to still commonly used array- and PCR-based methods, and look forward to the additional advantages of single-molecule sequencing. As the current bottleneck in epigenomics research is the analysis rather than generation of data, the basic difficulties and problem-solving strategies regarding data preprocessing and statistical analysis are introduced for the different technologies. Finally, we also consider the complications associated with epigenomic studies of species with yet unsequenced genomes and possible solutions. Environ. Mol. Mutagen. 55:155-170, 2014. (c) 2013 Wiley Periodicals, Inc.

关键词： sequencing histone modifications bioinformatics epigenetics epigenomics data analysis nucleosome positioning DNA methylation DNA hydroxymethylation noncoding rna

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Long-read rna sequencing can probe organelle genome pervasive transcription

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BRIEFINGS IN FUNCTIONAL GENOMICS 2024年第6期23卷 695-701页

作者： Lima, Matheus Sanita Silva Domingues, Douglas Rossi Paschoal, Alexandre Smith, David Roy Western Univ Dept Biol 1151 Richmond St London ON N6A 5B7 Canada Univ Sao Paulo Luiz de Queiroz Coll Agr Dept Genet Ave Padua Dias 11 BR-13418900 Piracicaba SP Brazil Fed Univ Technol Parana UTFPR Dept Comp Sci Bioinformat & Pattern Recognit Grp BIOINFO CP Ave Alberto Carazzai 1640 BR-86300000 Cornelio Procopio PR Brazil

40 years ago, organelle genomes were assumed to be streamlined and, perhaps, unexciting remnants of their prokaryotic past. However, the field of organelle genomics has exposed an unparallel diversity in genome architecture (i.e. genome size, structure, and content). The transcription of these eccentric genomes can be just as elaborate - organelle genomes are pervasively transcribed into a plethora of rna types. However, while organelle protein-coding genes are known to produce polycistronic transcripts that undergo heavy posttranscriptional processing, the nature of organelle noncoding transcriptomes is still poorly resolved. Here, we review how wet-lab experiments and second-generation sequencing data (i.e. short reads) have been useful to determine certain types of organelle rnas, particularly noncoding rnas. We then explain how third-generation (long-read) rna-Seq data represent the new frontier in organelle transcriptomics. We show that public repositories (e.g. NCBI SRA) already contain enough data for inter-phyla comparative studies and argue that organelle biologists can benefit from such data. We discuss the prospects of using publicly available sequencing data for organelle-focused studies and examine the challenges of such an approach. We highlight that the lack of a comprehensive database dedicated to organelle genomics/transcriptomics is a major impediment to the development of a field with implications in basic and applied science.

关键词： long-read rna sequencing pervasive transcription noncoding rna organelle genome mitochondrial transcription plastid transcription

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A large-scale full-length cDNA analysis to explore the budding yeast transcriptome

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006年第47期103卷 17846-17851页

作者： Miura, Fumihito Kawaguchi, Noriko Sese, Jun Toyoda, Atsushi Hattori, Masahira Morishita, Shinichi Ito, Takashi Univ Tokyo Grad Sch Frontier Sci Dept Computat Biol Kashiwa Chiba 2778561 Japan Japan Sci & Technol Agcy Inst Bioinformat Res & Dev Tokyo 1020081 Japan RIKEN Yokohama Inst Inst Phys & Chem Res Genom Sci Ctr Yokohama Kanagawa 2300045 Japan Kitasato Univ Kitasato Inst Life Sci Tokyo 1088641 Japan

We performed a large-scale cDNA analysis to explore the transcriptome of the budding yeast Saccharomyces cerevisiae. We sequenced two cDNA libraries, one from the cells exponentially growing in a minimal medium and the other from meiotic cells. Both libraries were generated by using a vector-capping method that allows the accurate mapping of transcription start sites (TSSs). Consequently, we identified 11,575 TSSs associated with 3,638 annotated genomic features, including 3,599 ORFs, to suggest that most yeast genes have two or more TSSs. In addition, we identified 45 previously undescribed introns, including those affecting current ORF annotations and those spliced alternatively. Furthermore, the analysis revealed 667 transcription units in the intergenic regions and transcripts derived from antisense strands of 367 known features. We also found that 348 ORFs carry TSSs in their 3'-halves to generate sense transcripts starting from inside the ORFs. These results indicate that the budding yeast transcriptome is considerably more complex than previously thought, and it shares many recently revealed characteristics with the transcriptomes of mammals and other higher eukaryotes. Thus, the genome-wide active transcription that generates novel classes of transcripts appears to be an intrinsic feature of the eukaryotic cells. The budding yeast will serve as a versatile model for the studies on these aspects of transcriptome, and the full-length cDNA clones can function as an invaluable resource in such studies.

关键词： alternative splicing antisense transcript noncoding rna transcription start site

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Identification of differentially expressed circular rnas in chemoresistant colorectal cancer

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EPIGENOMICS 2019年第8期11卷 875-884页

作者： Abu, Nadiah Hon, Kha Wai Jeyaraman, Shivapriya Yahaya, Azyani Abdullah, Nik M. A. Mustangin, Muaatamarulain Sulaiman, Siti A. Jamal, Rahman Ab-Mutalib, Nurul-S Univ Kebangsaan Malaysia UKM Med Mol Biol Inst UMBI Kuala Lumpur 56000 Malaysia Univ Kebangsaan Malaysia Dept Pathol Fac Med UKM Med Ctr Kuala Lumpur 56000 Malaysia Univ Kebangsaan Malaysia Dept Oncol & Radiotherapy Fac Med UKM Med Ctr Kuala Lumpur 56000 Malaysia

Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular rnas (circrnas) are a type of noncoding rna that were found to be important in cellular homeostasis. The involvement of circrnas in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circrnas between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circrnas via microarray. We further validated the expression of two circrnas in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR). Results & conclusion: We found that there were 773 upregulated and 732 downregulated circrnas between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.

关键词： circrna circrna-mirna-m rna interaction colorectal cancer drug resistance 5-fluorouracil FOL-FOX HCT116 microarray noncoding rna oxaliplatin

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In silico determination of transposon-derived mirnas and targets in Aegilops species

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JOUrnaL OF BIOMOLECULAR STRUCTURE & DYNAMICS 2020年第10期38卷 3098-3109页

作者： Marakli, Sevgi Amasya Univ Sabuncuoglu Serefeddin Hlth Serv Vocat Sch Dept Med Serv & Tech TR-05100 Ipekkoy Amasya Turkey Amasya Univ Cent Res Lab Ipekkoy Amasya Turkey

Transposable elements (TEs) are found almost in all living organism, shaping organisms' genomes. mirnas are noncoding rna types which are especially important in gene expression regulations. Many previously determined plant mirnas are identical/homologous to transposons (TE-MIR). The aim of this study was computational characterization of novel TE-related mirnas and their targets in Aegilops genome by using stringent criteria. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed by BLAST2GO. Seventeen novel TE-related mirnas in Aegilops genome were identified for the first time. GO analyses indicated that 40 targets played different roles in biological processes, cellular components and molecular functions. Moreover, these genes were involved in 10 metabolic pathways such as purine metabolism, nitrogen metabolism, oxidative phosphorylation, etc. as a result of KEGG analyses. Identification of mirnas and their targets are significant to understand mirna-TEs relationships and even how TEs affect plant growth and development. Obtaining results of this study are expected to provide possible new insight into Aegilops and its related species, wheat, with respect to mirnas evolution and domestication. Communicated by Ramaswamy H. Sarma

关键词： Transposable elements noncoding rna gene ontology gene regulation

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