SEARCH · PubMed Health

Results for “MicroRNA, (miRNA)”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2005

MicroRNA biogenesis and cancer.

MicroRNAs (miRNA) are a recently discovered family of short non-protein-coding RNAs that negatively regulate gene expression. Recent studies of miRNAs highlight a requirement for cell viability. Posttranscriptional silencing of target genes by miRNAs occurs either by targeting specific cleavage of homologous mRNAs, or by targeting specific inhibition of protein synthesis. We recently identified a multisubunit protein complex termed Microprocessor that is necessary and sufficient for processing miRNA precursor RNAs. Microprocessor contains Drosha, an RNase III endonuclease, and DGCR8, a gene deleted in DiGeorge syndrome. We consider recent findings that link miRNA perturbation to cancer.

Humans↗

PubMed2006

MicroRNAs and genomic instability.

A new species of non-coding RNA, microRNAs (miRNAs) has been identified that may regulate the expression of as many as one third to one half of all protein encoding genes. MicroRNAs are found throughout mammalian genomes, but an association between the location of these miRNAs and regions of genomic instability (or fragile sites) in humans has been suggested [1]. In this review we discuss the possible role of altered miRNA expression on human cancer and conduct an analysis correlating the physical location of murine miRNAs with sites of genetic alteration in mouse models of cancer.

Animals↗

PubMed2005

Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis.

Small RNAs of 21-25 nucleotides (nt), including small interfering RNAs (siRNAs) and microRNAs (miRNAs), act as guide RNAs to silence target-gene expression in a sequence-specific manner. In addition to a Dicer homolog, DCL1, the biogenesis of miRNAs in Arabidopsis requires another protein, HEN1. miRNAs are reduced in abundance and increased in size in hen1 mutants. We found that HEN1 is a miRNA methyltransferase that adds a methyl group to the 3'-most nucleotide of miRNAs, but the role of miRNA methylation was unknown. Here, we show that siRNAs from sense transgenes, hairpin transgenes, and transposons or repeat sequences, as well as a new class of siRNAs known as trans-acting siRNAs, are also methylated in vivo by HEN1. In addition, we show that the size increase of small RNAs in the hen1-1 mutant is due to the addition of one to five U residues to the 3' ends of the small RNAs. Therefore, a novel uridylation activity targets the 3' ends of unmethylated miRNAs and siRNAs in hen1 mutants. We conclude that 3'-end methylation is a common step in miRNA and siRNA metabolism and likely protects the 3' ends of the small RNAs from the uridylation activity.

Amino Acid Sequence↗

PubMed2005

Post-transcriptional gene silencing by siRNAs and miRNAs.

Recent years have seen a rapid increase in our understanding of how double-stranded RNA (dsRNA) and 21- to 25-nucleotide small RNAs, microRNAs (miRNAs) and small interfering RNAs (siRNAs), control gene expression in eukaryotes. This RNA-mediated regulation generally results in sequence-specific inhibition of gene expression; this can occur at levels as different as chromatin modification and silencing, translational repression and mRNA degradation. Many details of the biogenesis and function of miRNAs and siRNAs, and of the effector complexes with which they associate have been elucidated. The first structural information on protein components of the RNA interference (RNAi) and miRNA machineries is emerging, and provides some insight into the mechanism of RNA-silencing reactions.

Animals↗

PubMed2005

Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally repress gene expression in animals and plants. A microarray profiling survey revealed the expression patterns of 175 human miRNAs across 24 different human organs. Our results show that proximal pairs of miRNAs are generally coexpressed. In addition, an abrupt transition in the correlation between pairs of expressed miRNAs occurs at a distance of 50 kb, implying that miRNAs separated by <50 kb typically derive from a common transcript. Some microRNAs are within the introns of host genes. Intronic miRNAs are usually coordinately expressed with their host gene mRNA, implying that they also generally derive from a common transcript, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic miRNAs.

Base Sequence↗

PubMed2003

Arabidopsis HEN1: a genetic link between endogenous miRNA controlling development and siRNA controlling transgene silencing and virus resistance.

In animals, double-stranded short interfering RNA (siRNA) and single-stranded microRNA (miRNA) regulate gene expression by targeting homologous mRNA for cleavage or by interfering with their translation, respectively. siRNAs are processed from injected or transgene-derived, long, perfect double-stranded RNA (dsRNA), while miRNAs are processed from short, imperfect dsRNA precursors transcribed from endogenous intergenic regions. In plants, both siRNAs and miRNAs activate cleavage of homologous RNA targets, but little is known about the genes controlling their production or action. The SGS2/SDE1 protein contributes to produce transgene siRNA, while DCL1 and HEN1 contribute to endogenous miRNA accumulation. Here, we show that: i) SGS2, SGS3, AGO1, and HEN1 contribute to produce transgene siRNA involved in sense posttranscriptional gene silencing (S-PTGS); ii) HEN1, but not SGS2, SGS3, or AGO1, contributes to the accumulation of the endogenous miR171 miRNA and to the cleavage of Scarecrow target mRNA by miR171; iii) SGS2, SGS3, AGO1, and HEN1 contribute to resistance against cucumber mosaic virus, but not to siRNA and IR-PTGS triggered by hairpin transgenes directly producing perfect dsRNA; and iv) the actions of HEN1 in miRNA/development and siRNA/S-PTGS can be uncoupled by single-point mutations at different positions in the protein.

Arabidopsis↗

PubMed2026

Invertebrate miRNA pva-small RNA-11881/pva-miR-11881 as a potential RNA-based therapeutic against white spot syndrome virus in infected shrimp.

Small RNAs and microRNAs (miRNAs) play diverse roles in host virus interactions and hold promise for therapeutic applications. An uncharacterized shrimp miRNA with potent activity against white spot syndrome virus (WSSV), a major double-stranded DNA pathogen in aquaculture, was identified and characterized. Among the 1,239 differentially expressed unannotated small RNAs in Penaeus vannamei hemocytes, one of the most strongly downregulated candidates, termed pva-small RNA-11881 or pva-miR-11881, was predicted to target multiple WSSV genes. A pva-small RNA-11881/pva-miR-11881 isomir that originates from the 5' untranslated region of a host lipase 3-like gene was identified. Its primary transcript contains Drosha and Dicer processing sites, and the precursor exhibits canonical pre-miRNA features. In vivo administration of its primary transcript, pva-pri-miR-11881, significantly reduced WSSV copy number and improved shrimp survival. Mechanistically, pva-miR-11881 directly suppresses crucial WSSV genes WSSV004, WSSV164, and WSSV419 and modulates the host immune response against WSSV infection by enhancing phenoloxidase activity, thereby reducing apoptosis and necrosis, and promoting caspase-1-mediated cell death. These findings reveal that the pva-miR-11881 in P. vannamei holds strong potential as a biotherapeutic agent for managing viral diseases in shrimp.

Animals↗

PubMed2004

Managing the genome: microRNAs in Drosophila.

MicroRNAs (miRNAs) represent a growing class of short non-coding RNAs that regulate gene expression by post-transcriptional mechanisms. By binding to target mRNAs via stretches of sequence complementarity, microRNAs inhibit the production of target proteins or induce degradation of mRNAs. Several hundred miRNAs have recently been predicted and cloned from eukaryotic organisms as diverse as plants, invertebrates, and vertebrates. Some miRNAs were shown to be widely conserved across phyla. However, except in a few described cases, rather little is known about their endogenous target genes and the physiological pathways they impinge on. Invertebrate model organisms such as C. elegans and Drosophila have been instrumental to develop methods and to dissect biological roles of miRNAs. In this review, we will focus on recent progress in characterizing miRNAs and steps toward identification of target genes in Drosophila. Many of these recent experiments provide evidence that a systematic target discovery is feasible and that the biology of miRNAs can be functionally explored using forward and reverse genetic tools.

Animals↗

PubMed2026

Diagnostic and Predictive Value of Circulating and Exosomal microRNAs in Ferroptosis-Associated Neurological Conditions: A Systematic Review and Meta-analysis.

Circulating microRNAs (miRNAs) have emerged as potential non-invasive markers for intracranial pathology, yet their diagnostic accuracy and relationship with ferroptosis-mediated neuronal damage remain poorly defined. The primary objective of this study was to evaluate the diagnostic and predictive potential of circulating and exosomal miRNAs across ferroptosis-associated neurological conditions and to explore their associations with ferroptosis-related pathways. Following PRISMA-DTA guidelines, a systematic literature search was conducted across PubMed, Scopus, Cochrane, and ScienceDirect, identifying 205 records. After screening for human clinical cohort validation, 7 studies were included in the qualitative synthesis and 5 in the quantitative meta-analysis. Pooled Area-under-the-Curve (AUC) was calculated using a random-effects inverse-variance model, while prognostic correlation coefficients (r) were synthesized using Fisher's Z-transformation. Methodological quality was assessed via QUADAS-2. Analysis of 7 clinical cohorts provided heterogeneous evidence on the diagnostic and prognostic potential of miRNAs. Random-effects pooling of the two eligible diagnostic AUC estimates yielded an exploratory pooled AUC of 0.87 (95% CI, 0.79-0.94; I2 .90%). Prognostic synthesis of Group 2 identified an exploratory association between miRNA levels and clinical severity scales (exploratory pooled correlation coefficient of 0.67 (95% CI: 0.56-0.76; I2 .714.4%). Selected miRNAs were mapped to ferroptosis-associated regulators, including SLC7A11, ABCB8, and SLC40A1. Exosomal miRNAs hold potential to indicate disease-associated molecular information, although comparative clinical evidence remains yet to be explored. Circulating and exosomal miRNAs show promising diagnostic and prognostic potential across selected neurological conditions. These findings highlight a potential mechanistic association between miRNA expression and ferroptosis-mediated neuronal injury.

Humans↗

PubMed2003

Macro effects of microRNAs in plants.

MicroRNAs (miRNAs) are 20- to 22-nucleotide fragments that regulate expression of mRNAs that have complementary sequences. They are numerous and widespread among eukaryotes, being conserved throughout evolution. The few miRNAs that have been fully characterized were found in Caenorhabditis elegans and are required for development. Recently, a study of miRNAs isolated from Arabidopsis showed that here also developmental genes are putative regulatory targets. A role for miRNAs have in plant development is supported by the developmental phenotypes of mutations in the genes required for miRNA processing.

Gene Expression Regulation, Plant↗

PubMed2026

miRNA-mediated control of TLR-NLR interplay in the uterus: A hidden corner of recurrent pregnancy loss.

Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are crucial pattern recognition receptors that initiate inflammatory responses and immunological activation upon detecting pathogen- or damage-associated molecular patterns (PAMPs/DAMPS) in the female reproductive tract, thereby maintaining homeostasis and supporting pregnancy success. Their signaling pathways play a significant role in reproductive disorders by mediating the immune response to various pathogenic stimuli. Recurrent pregnancy loss (RPL), defined as the natural ending of two or more pregnancies before 24 weeks of gestation, approximately half of these patients remain idiopathic without precise prognostic, diagnostic, and therapeutic plans. Emerging data point that microRNAs are essential for immunological control in the female reproductive tract. MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to mRNA and preventing translation into protein. miRNAs play a role in many biological processes, including the development and differentiation of trophoblasts, the activation and implantation of embryos, immune tolerance, and the receptivity of the endometrium during implantation. Given their capacity to regulate up to 30 % of the human genome, miRNAs offer a promising avenue for understanding the immunopathogenesis of pregnancy complications. Recent research has detected differential expression of specific miRNAs in reproductive system pathologies. This review focuses on microRNAs and their association with idiopathic recurrent miscarriage, a condition characterized by considerable heterogeneity. Future studies identifying the precise mechanisms linking miRNA-mediated immune dysregulation in RPL immunopathogenesis could open the way for novel personalized therapeutic and diagnostic strategies.

Female↗

PubMed2026

Integrative methylation and miRNA dysregulation in dlPFC reveal distinct molecular signatures of suicide and non-suicide subtypes in major depressive disorder.

AIM: Major depressive disorder (MDD) is a leading cause of disability and carries a high risk of suicide. MicroRNAs (miRNAs) are epigenetic regulators implicated in MDD and can be regulated by DNA methylation, potentially reshaping downstream gene networks. We investigated methylation-linked miRNA dysregulation and explored whether these changes are specifically associated with suicide among MDD patients. METHODS: Genome-wide DNA methylation profiling of the dorsolateral prefrontal cortex from 15 MDD patients who died by suicide (MDD+S), 17 MDD patients who died from causes other than suicide (MDD-S), and 16 controls (C) using the Illumina 850K MethylationEPIC array was integrated with small RNA sequencing-based miRNA quantification to identify miRNA-associated differentially methylated probes (DMPs), link methylation to miRNA expression, and infer downstream targets and pathways. RESULTS: Differential methylation analysis (P ≤ 0.05) revealed 139 miRNA-linked DMPs in C vs. MDD+/-S, 135 in C vs. MDD-S, 179 in C vs. MDD+S, and the highest in MDD+S vs. MDD-S (235). CpG-miRNA pairing (within 1500kb promoter) followed by Spearman correlation identified inverse associations between CpG β values and miRNA expression, with the most consistent signals in suicide-status-stratified subsets, including cg06341821-hsa-miR-574-3p and cg25451306-hsa-miR-2110 in MDD+S-related contrasts, and cg06179179-hsa-miR-595 in MDD-S-related contrasts. High-confidence target prediction and ClueGO enrichment indicated distinct biology: miR-595 target genes in MDD-S were enriched for interferon/innate immune signaling, whereas miR-2110 target genes in MDD+S were enriched for ligand-gated ion channel activity and synaptic/receptor signaling. CONCLUSION: This integrated approach identifies methylation-regulated miRNA pathways that may play key roles in the molecular pathogenesis of MDD and suicide.

Humans↗

PubMed2026

Small-Molecule Degradation of the MicroRNA-21 Precursor Rescues Pathogenic Pathways in Cellular Models of Fibrosis.

MicroRNAs (miRNAs) are short RNA molecules that bind to target mRNAs, resulting in translational repression and gene silencing. Overexpression of microRNA-21 (miR-21) is associated with various human diseases, including autosomal dominant polycystic kidney disease (ADPKD) and pulmonary fibrosis. In this study, a previously described heterobifunctional molecule, TGP-21-RiboTAC, that degrades the miR-21 precursor (pre-miR-21) in triple-negative breast cancer cells was investigated in polycystic kidney cell lines and a lung fibroblast cell line. In the former, TGP-21-RiboTAC degraded pre-miR-21 and derepressed miR-21's downstream targets, programmed cell death 4 (PDCD4) and peroxisome proliferator-activated receptor alpha (PPARα), known drivers of ADPKD. The heterobifunctional molecule also inhibited cyst growth and rescued the metabolic alterations that occur in ADPKD. In the lung fibroblast cell line, MRC-5, TGP-21-RiboTAC also reduced pre- and mature miR-21 levels, rescued transforming growth factor β (TGF-β)-induced repression of SMAD family member 7 (SMAD7), and inhibited cell invasion. Collectively, these studies demonstrate the potential of targeted RNA degradation as therapeutic agents that retard the development of organ fibrosis.

MicroRNAs↗

PubMed2006

Signalling between the shoot apical meristem and developing lateral organs.

A characteristic feature of plant development is the extensive role played by cell-cell signalling in regulating patterns of growth and cell fate. This is particularly apparent in the shoot apical meristem (SAM) where signalling is involved in the maintenance of a central undifferentiated stem cell population and the formation of a regular and predictable pattern of leaves, from the meristem periphery. Although these two functions occur in different regions of the meristem, their activity must be coordinated to maintain meristem integrity. The role of signalling in the SAM was first characterised over 60 years ago by elegant surgical experiments. These studies showed that existing leaf primordia determine future sites of organ formation in adjacent regions of the SAM, a finding that laid the foundation for subsequent studies into the mechanisms controlling phyllotaxy. Recent studies have identified auxin as a likely signal promoting organ formation and shown that young primordia play an important role in determining its distribution in the SAM. These pioneering surgical experiments also revealed that signals from the meristem regulate the development of organ primordia. In this case a meristem signal promotes the formation of cell types found in the top/adaxial half of the emerging leaf. While the identity of this signal remains elusive, the recent characterisation of a small family of PHABULOSA-like (PHB-like) transcription factor genes has provided important clues to its nature. These genes, which promote adaxial cell identity, are regulated by microRNAs (miRNAs) raising the exciting possibility that the meristem signal is either a miRNA or part of a pathway regulating the distribution of miRNAs.

Body Patterning↗

PubMed2006

Primate microRNAs miR-220 and miR-492 lie within processed pseudogenes.

MicroRNAs (miRNAs) are a new and abundant class of small, noncoding RNAs. To date, the evolutionary history of most of these loci appears to be marked by duplication and divergence. The ultimate origin of miRNAs remains an open question. A survey of the genomic context of more than 300 human miRNA loci revealed that two primate-specific miRNAs, miR-220 and miR-492, each lie within a processed pseudogene. In silico and in vitro examinations of these two loci suggest that this is a rare phenomenon requiring the juxtaposition of a specific combination of factors. Thus it appears that, while processed pseudogenes are good candidates for miRNA incubators, it is unlikely that more than a very small percentage of new miRNAs arise this way.

Animals↗

PubMed2005

Targets for human encoded microRNAs in HIV genes.

MicroRNAs (miRNAs) are increasingly being shown to play vital roles in development, apoptosis, and oncogenesis by interfering with gene expression at the post-transcriptional level. miRNAs, in principle, can contribute to the repertoire of host pathogen interactions during HIV-1 infection. Using a consensus scoring approach, high scoring miRNA-target pairs were selected which were identified by four well-established target prediction softwares. While hsa-mir-29a and 29b target the nef gene, hsa-mir-149 targets the vpr gene, hsa-mir-378 targets env, and hsa-mir-324-5p targets the vif gene. Not only were the minimum free energy values lowest for the bound complex, but also, the rules so far observed for microRNA-target pairing, viz., a continuous stretch of 6-7 base pairing towards the 5' end of the miRNA and incomplete complementarity with the target sequence, were found to be valid. The target regions were highly conserved across the various clades of HIV-1. microRNA expression profiles from previously reported microarray based experiments show that the five human miRNAs are expressed in T-cells, the normal site of infection of HIV-1 virus. This is the first report of human microRNAs which can target crucial HIV-1 genes including the nef gene, which plays an important role in delayed disease progression.

Base Pairing↗

PubMed2006

Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance.

Chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in the Western world, is characterized by predominantly nondividing malignant CD5+ B cells overexpressing the anti-apoptotic Bcl2 protein. Significant familial aggregation with largely unknown mode of inheritance has been demonstrated. Until recently little else was known regarding the events leading to CLL initiation and progression. New findings support the view that CLL is a genetic disease where the main alterations occur at the level of transcriptional/post-transcriptional regulation of the malignant cells genome because of deregulations of a new class of genes named microRNAs (miRNAs). miRNA genes miR-15a and miR-16-1, located at 13q14.3, are frequently deleted and/or downregulated in patients with B-cell CLL. Both microRNAs negatively regulate Bcl2 at a post-transcriptional level and this repression is enough to induce apoptosis. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors. Furthermore, microRNA expression profiles can distinguish normal B cells from malignant B cells in CLL. A unique microRNA signature is associated with prognostic factors such as mutations in the immunoglobulin heavy-chain variable-region gene (IgV(H)) or high expression of the 70-kd zeta-associated protein (ZAP-70+) and disease progression in CLL. Mutations in miRNA transcripts are frequent, some of them germ-line, and may have functional importance and may predispose to CLL and to a spectrum of associated malignancies.

Animals↗

PubMed2005

Extensive modulation of a set of microRNAs in primary glioblastoma.

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules may represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme, the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly up-regulated in glioblastoma and from a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, and miR-181c, which are down-regulated in glioblastoma.

Brain↗