scholarly journals Translational applications of microRNA genes in medulloblastomas

2010 ◽  
Vol 33 (4) ◽  
pp. 223 ◽  
Author(s):  
Norbert F Ajeawung ◽  
Bin Li ◽  
Deepak Kamnasaran
Keyword(s):  
Biological Significance ◽  
Clinical Importance ◽  
Molecular Classification ◽  
Qualitative Assessment ◽  
Normal Brain ◽  
Protein Coding ◽  
Rna Molecules ◽  
Mirna Genes ◽  
Molecular Events ◽  
Microrna Genes

Purpose: To provide a critical assessment of the clinical translational applications of microRNA (miRNA) genes in medulloblastomas. Methods: Data were obtained from MEDLINE using Boolean-formatted keyword queries. Top articles were selected for critical analyses - depending on the novelty of findings, qualitative assessment of the citation index and relevance to the diagnosis, prognosis and therapeutic targeting of medulloblastomas. Results: MiRNAs, non-protein-coding RNA molecules, negatively regulate gene expression in a sequence–specific manner during biological processes. In the past few years, miRNA genes have emerged as key regulators of not only molecular events involved in normal brain development and function but also in the molecular pathogenesis of medulloblastomas. In this manner, microRNA genes are identified with functional roles as oncogenes and tumor suppressor genes. At least four miRNAs have proven useful in improving the molecular classification of medulloblastomas, and eight others have shown potential in predicting patients’ overall prognosis. Moreover, more than 10 miRNA genes can be potentially utilized in therapies against medulloblastomas, using nine recent methods of targetting miRNAs. Conclusion: The quest to identify miRNA genes that are of biological significance in medulloblastomas is on an ongoing venture. Most importantly, these miRNAs have been shown to be of clinical importance for improving the accuracy of diagnosis and prognosis and even developing therapies that can significantly improve patients’ overall survival from this deadly disease.

scholarly journals Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Biological Significance ◽  
Rna Seq ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

scholarly journals NOVOMIR: De Novo Prediction of MicroRNA-Coding Regions in a Single Plant-Genome

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Jan-Hendrik Teune ◽  
Gerhard Steger
Keyword(s):  
Noncoding Rna ◽  
De Novo ◽  
Plant Genome ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Coding Regions ◽  
Mirna Genes ◽  
Genomic Scale ◽  
Eukaryotic Genomes

MicroRNAs (miRNA) are small regulatory, noncoding RNA molecules that are transcribed as primary miRNAs (pri-miRNA) from eukaryotic genomes. At least in plants, their regulatory activity is mediated through base-pairing with protein-coding messenger RNAs (mRNA) followed by mRNA degradation or translation repression. We describeNOVOMIR, a program for the identification of miRNA genes in plant genomes. It uses a series of filter steps and a statistical model to discriminate a pre-miRNA from other RNAs and does rely neither on prior knowledge of a miRNA target nor on comparative genomics. The sensitivity and specificity ofNOVOMIR for detection of premiRNAs fromArabidopsis thalianais ~0.83 and ~0.99, respectively. Plant pre-miRNAs are more heterogeneous with respect to size and structure than animal pre-miRNAs. Despite these difficulties,NOVOMIR is well suited to perform searches for pre-miRNAs on a genomic scale.NOVOMIR is written in Perl and relies on two additional, free programs for prediction of RNA secondary structure (RNALFOLD, RNASHAPES).

scholarly journals Polymorphisms in MicroRNA Genes Associated with Schizophrenia Susceptibility but Not with Effectiveness of MECT

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Danwei Zhang ◽  
Huihua Li ◽  
Kaimo Ding ◽  
Zhen Zhang ◽  
Si Luo ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Psychiatric Disease ◽  
Nucleotide Polymorphisms ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Mirna Genes ◽  
Potential Association ◽  
Syndrome Scale ◽  
Modified Electroconvulsive Therapy ◽  
Microrna Genes

Schizophrenia (SCZ) is a common and complex psychiatric disease associated with hereditary and environmental risk factors. MicroRNAs (miRNAs or miRs) are small, noncoding RNA molecules that endogenously regulate gene expression. Single nucleotide polymorphisms (SNPs) in related miRNA genes are associated with susceptibility of the disorder. We wonder if the SNPs have influence on the effectiveness of modified electroconvulsive therapy (MECT) for SCZ. rs1625579 within miR-137, rs6577555 within miR-34, and rs2296616 within miR-107 were sequenced in 150 cases and 150 controls to check the potential association between the SNPs and SCZ. Our results showed that allele G in rs1625579 ( p = 0.005 , adjusted   OR = 1.379 , 95 % CI = 1.108 − 1.634 ), allele A in rs6577555 ( p = 0.014 , adjusted   OR = 1.246 , 95 % CI = 1.045 − 1.463 ), allele G in rs2296616 ( p < 0.001 , adjusted   OR = 1.646 , 95 % CI = 1.374 − 1.879 ) are positively associated with the disorder risk. MECT courses did significantly decrease the level of the miRNAs, except for the variant of rs2296616 with the AA genotype. Schizophrenic phenotypes assessed by the positive and negative syndrome scale (PANSS) were improved after MECT, and there was no significant relevance observed between the effectiveness of MECT and the variants of these loci. Thus, our findings indicate that polymorphisms within the loci may be involved in the pathogenesis of SCZ, and MECT is effective and unbiased for patients harboring different genotypes of the loci.

scholarly journals Role of methylation of MIR-129-2, MIR-9-1, MIR-9-3, MIR-130b, MIR-107, and MIR-1258 miRNA genes in the pathogenesis and progression of breast cancer

2018 ◽  
pp. 115-118
Author(s):  
Е.А. Филиппова ◽  
А.М. Бурдённый ◽  
С.С. Лукина ◽  
И.В. Пронина ◽  
Т.П. Казубская ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Regional Lymph Nodes ◽  
Protein Coding ◽  
Specific Pcr ◽  
Mirna Genes ◽  
Progression Of Disease ◽  
Microrna Genes ◽  
Selection Of

Согласно последним эпигеномным исследованиям, доля гиперметилируемых генов микроРНК в несколько раз выше доли белок-кодирующих генов, что делает их перспективными маркерами опухолей. Цель исследования - обнаружение новых генов микроРНК, изменяющих уровень метилирования при раке молочной железы, и изучение их связь с развитием заболевания. Для 5 из 6 исследованных генов микроРНК: MIR-1258, -130b, -9-1, -9-3, -129-2 - методом метилспецифичной ПЦР отмечено статистически значимое (p < 0,01) повышение частот метилирования в 70 образцах опухолей молочной железы в сравнении с гистологически неизмененной тканью той же пациентки. Установлены значимые (p < 0,05) ассоциации частот метилирования 3 генов с такими параметрами прогрессии рака, как более тяжелая стадия (III-IV) рака (MIR-9-3 и MIR-1258), низкий уровень дифференцировки (MIR-107 и MIR-1258), размер опухоли (MIR-9-3), метастазы в регионарных лимфатических узлах и отдаленные метастазы (MIR-1258). Выявленные особенности метилирования исследованных генов могут найти клиническое применение для разработки современных подходов к профилактике, прогнозированию и выбору тактики лечения РМЖ. Epigenome studies have shown that the proportion of hypermethylated microRNA genes is several times higher than of protein-coding genes, which makes them promising markers of tumors. The aim of this study was to expand the spectrum of the miRNA genes hypermethylated in breast cancer and to investigate their connection with progression of disease. The methylation-specific PCR performed on a set of 70 breast cancer samples showed a significant increase in methylation frequency in tumor samples compared with histologically unchanged breast tissue for 5 of 6 studied microRNA genes - MIR-1258, -130b, -9-1, -9-3, and -129-2 (p < 0.01). Statistically significant (p < 0.05) associations of hypermethylation of 3 genes with parameters of cancer progression were established: for the MIR-9-3 and MIR-1258 genes - with more severe stages (III-IV) of cancer; MIR-107 and MIR-1258 - with a low level of tumor differentiation; MIR-9-3 - with tumor size; MIR-1258 - with metastases to regional lymph nodes or distant organs. The identified methylation features of the studied genes can find clinical application in development of modern approaches to prediction, prevention, and selection of tactics for the treatment of breast cancer.

scholarly journals MicroRNA Promoter Identification inArabidopsisUsing Multiple Histone Markers

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yuming Zhao ◽  
Fang Wang ◽  
Liran Juan
Keyword(s):  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Promoter Regions ◽  
Protein Coding ◽  
Next Generation Sequencing Technology ◽  
Small Noncoding Rna ◽  
Transcription Start Sites ◽  
Mirna Genes ◽  
Microrna Genes

A microRNA is a small noncoding RNA molecule, which functions in RNA silencing and posttranscriptional regulation of gene expression. To understand the mechanism of the activation of microRNA genes, the location of promoter regions driving their expression is required to be annotated precisely. Only a fraction of microRNA genes have confirmed transcription start sites (TSSs), which hinders our understanding of the transcription factor binding events. With the development of the next generation sequencing technology, the chromatin states can be inferred precisely by virtue of a combination of specific histone modifications. Using the genome-wide profiles of nine histone markers including H3K4me2, H3K4me3, H3K9Ac, H3K9me2, H3K18Ac, H3K27me1, H3K27me3, H3K36me2, and H3K36me3, we developed a computational strategy to identify the promoter regions of most microRNA genes inArabidopsis, based upon the assumption that the distribution of histone markers around the TSSs of microRNA genes is similar to the TSSs of protein coding genes. Among 298 miRNA genes, our model identified 42 independent miRNA TSSs and 132 miRNA TSSs, which are located in the promoters of upstream genes. The identification of promoters will provide better understanding of microRNA regulation and can play an important role in the study of diseases at genetic level.

scholarly journals Normal tissue content impact on the GBM molecular classification

2020 ◽  
Author(s):  
Rodrigo Madurga ◽  
Noemí García-Romero ◽  
Beatriz Jiménez ◽  
Ana Collazo ◽  
Francisco Pérez-Rodríguez ◽  
...  
Keyword(s):  
Normal Tissue ◽  
In Silico Analysis ◽  
Molecular Classification ◽  
Gene Signature ◽  
Normal Brain ◽  
Normal Cells ◽  
Final Model ◽  
Tumor Subtypes ◽  
Tissue Content

Abstract Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.

scholarly journals Disrupting upstream translation in mRNAs is associated with human disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David S. M. Lee ◽  
Joseph Park ◽  
Andrew Kromer ◽  
Aris Baras ◽  
Daniel J. Rader ◽  
...  
Keyword(s):  
Protein Expression ◽  
Biological Significance ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Protein Coding ◽  
Stop Codons ◽  
Human Genes ◽  
Strong Negative Selection ◽  
Disease Associations ◽  
Reading Frames

AbstractRibosome-profiling has uncovered pervasive translation in non-canonical open reading frames, however the biological significance of this phenomenon remains unclear. Using genetic variation from 71,702 human genomes, we assess patterns of selection in translated upstream open reading frames (uORFs) in 5’UTRs. We show that uORF variants introducing new stop codons, or strengthening existing stop codons, are under strong negative selection comparable to protein-coding missense variants. Using these variants, we map and validate gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals, respectively, and elucidate their impact on protein expression in human cells. Our results suggest translation disrupting mechanisms relating uORF variation to reduced protein expression, and demonstrate that translation at uORFs is genetically constrained in 50% of human genes.

scholarly journals Topography of transcriptionally active chromatin in glioblastoma

2021 ◽  
Vol 7 (18) ◽  
pp. eabd4676
Author(s):  
Liang Xu ◽  
Ye Chen ◽  
Yulun Huang ◽  
Edwin Sandanaraj ◽  
John S. Yu ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Molecular Classification ◽  
Normal Brain ◽  
Active Chromatin ◽  
Primary Tumors ◽  
Genomic Variations ◽  
Transcriptional Enhancers ◽  
Super Enhancer ◽  
Druggable Targets ◽  
Regulatory Landscapes

Molecular profiling of the most aggressive brain tumor glioblastoma (GBM) on the basis of gene expression, DNA methylation, and genomic variations advances both cancer research and clinical diagnosis. The enhancer architectures and regulatory circuitries governing tumor-intrinsic transcriptional diversity and subtype identity are still elusive. Here, by mapping H3K27ac deposition, we analyze the active regulatory landscapes across 95 GBM biopsies, 12 normal brain tissues, and 38 cell line counterparts. Analyses of differentially regulated enhancers and super-enhancers uncovered previously unrecognized layers of intertumor heterogeneity. Integrative analysis of variant enhancer loci and transcriptome identified topographies of transcriptional enhancers and core regulatory circuitries in four molecular subtypes of primary tumors: AC1-mesenchymal, AC1-classical, AC2-proneural, and AC3-proneural. Moreover, this study reveals core oncogenic dependency on super-enhancer–driven transcriptional factors, long noncoding RNAs, and druggable targets in GBM. Through profiling of transcriptional enhancers, we provide clinically relevant insights into molecular classification, pathogenesis, and therapeutic intervention of GBM.

Dual Isoform Sequencing Reveals a Multifaceted Transcriptional Architecture of a Prototype Baculovirus

2021 ◽  
Author(s):  
Gábor Torma ◽  
Dóra Tombácz ◽  
Norbert Moldován ◽  
Ádám Fülöp ◽  
István Prazsák ◽  
...  
Keyword(s):  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Oxford Nanopore ◽  
The Pacific ◽  
Viral Genes ◽  
Long Read ◽  
Oxford Nanopore Technologies ◽  
Overlapping Transcripts

Abstract In this study, we used two long-read sequencing (LRS) techniques, Sequel from the Pacific Biosciences and MinION from Oxford Nanopore Technologies, for the transcriptional characterization of a prototype baculovirus, Autographacalifornica multiple nucleopolyhedrovirus. LRS is able to read full-length RNA molecules, and thereby to distinguish between transcript isoforms, mono- and polycistronic RNAs, and overlapping transcripts. Altogether, we detected 875 transcripts, of which 759 are novel and 116 have been annotated previously. These RNA molecules include 41 novel putative protein coding transcript (each containing 5’-truncated in-frame ORFs), 14 monocistronic transcripts, 99 multicistronic RNAs, 101 non-coding RNA, and 504 length isoforms. We also detected RNA methylation in 12 viral genes and RNA hyper-editing in the longer 5’-UTR transcript isoform of ORF 19 gene.

scholarly journals Sequencing of small RNAs of the fern Pleopeltis minima (Polypodiaceae) offers insight into the evolution of the microRNA repertoire in land plants

2016 ◽  
Author(s):  
Florencia Berruezo ◽  
Flavio S. J. de Souza ◽  
Pablo I. Picca ◽  
Sergio I. Nemirovsky ◽  
Leandro Martinez-Tosar ◽  
...  
Keyword(s):  
Small Rna ◽  
Land Plant ◽  
Land Plants ◽  
Phylogenetic Position ◽  
Seed Plants ◽  
Messenger Rnas ◽  
Rna Molecules ◽  
Functional Studies ◽  
Mirna Genes ◽  
Ecological Importance

AbstractMicroRNAs (miRNAs) are short, single stranded RNA molecules that regulate the stability and translation of messenger RNAs in diverse eukaryotic groups. Several miRNA genes are of ancient origin and have been maintained in the genomes of animal and plant taxa for hundreds of millions of years, and functional studies indicate that ancient miRNAs play key roles in development and physiology. In the last decade, genome and small RNA (sRNA) sequencing of several plant species have helped unveil the evolutionary history of land plant miRNAs. Land plants are divided into bryophytes (liverworts, mosses), lycopods (clubmosses and spikemosses), monilophytes (ferns and horsetails), gymnosperms (cycads, conifers and allies) and angiosperms (flowering plants). Among these, the fern group occupies a key phylogenetic position, since it represents the closest extant cousin taxon of seed plants, i.e. gymno- and angiosperms. However, in spite of their evolutionary, economic and ecological importance, no fern genome has been sequenced yet and few genomic resources are available for this group. Here, we sequenced the small RNA fraction of an epiphytic South American fern, Pleopeltis minima (Polypodiaceae), and compared it to plant miRNA databases, allowing for the identification of miRNA families that are shared by all land plants, shared by all vascular plants (tracheophytes) or shared by euphyllophytes (ferns and seed plants) only. Using the recently described transcriptome of another fern, Lygodium japonicum, we also estimated the degree of conservation of fern miRNA targets in relation to other plant groups. Our results pinpoint the origin of several miRNA families in the land plant evolutionary tree with more precision and are a resource for future genomic and functional studies of fern miRNAs.

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