PubMed Health⌕ Search

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 685 records · Page 38Linked to original sources

CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana.

BACKGROUND: In metazoans, microRNAs, or miRNAs, constitute a growing family of small regulatory RNAs that are usually 19-25 nucleotides in length. They are processed from longer precursor RNAs that fold into stem-loop structures by the ribonuclease Dicer and are thought to regulate gene expression by base pairing with RNAs of protein-coding genes. In Arabidopsis thaliana, mutations in CARPEL FACTORY (CAF), a Dicer homolog, and those in a novel gene, HEN1, result in similar, multifaceted developmental defects, suggesting a similar function of the two genes, possibly in miRNA metabolism. RESULTS: To investigate the potential functions of CAF and HEN1 in miRNA metabolism, we aimed to isolate miRNAs from Arabidopsis and examine their accumulation during plant development in wild-type plants and in hen1-1 and caf-1 mutant plants. We have isolated 11 miRNAs, some of which have potential homologs in tobacco, rice, and maize. The putative precursors of these miRNAs have the capacity to form stable stem-loop structures. The accumulation of these miRNAs appears to be spatially or temporally controlled in plant development, and their abundance is greatly reduced in caf-1 and hen1-1 mutants. HEN1 homologs are found in bacterial, fungal, and metazoan genomes. CONCLUSIONS: miRNAs are present in both plant and animal kingdoms. An evolutionarily conserved mechanism involving a protein, known as Dicer in animals and CAF in Arabidopsis, operates in miRNA metabolism. HEN1 is a new player in miRNA accumulation in Arabidopsis, and HEN1 homologs in metazoans may have a similar function. The developmental defects associated with caf-1 and hen1-1 mutations and the patterns of miRNA accumulation suggest that miRNAs play fundamental roles in plant development.

Amino Acid Sequence↗

MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation.

Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTLs, and that deletion or depletion of Dicer in mouse or human activated CD8(+) T cells causes up-regulation of perforin, granzymes, and effector cytokines. Genome-wide analysis of microRNA (miR, miRNA) changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of an miRNA network that controls perforin, eomesodermin, and IL-2Rα expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation, and antigenic stimulation. Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation.

Adoptive Transfer↗

The microRNA Registry.

The miRNA Registry provides a service for the assignment of miRNA gene names prior to publication. A comprehensive and searchable database of published miRNA sequences is accessible via a web interface (http://www.sanger.ac.uk/Software/Rfam/mirna/), and all sequence and annotation data are freely available for download. Release 2.0 of the database contains 506 miRNA entries from six organisms.

Animals↗

[Great potential of small RNAs: RNA interference and microRNA].

Double-stranded RNA (dsRNA) induces a sequence-specific silencing in eukaryotic cells. This silencing process beggins when long dsRNA is cleaved to 21 to 26 long small RNA by means of the RNAse III-type enzyme Dicer. These small dsRNA are included into silencing effector complexes, that are targeted to complementary sequences. Small RNA dependent gene silencing can be achieved by distinct mechanisms based depending mainly on the nature of target sequences and on the proteins present in the effector complex. The route of interference RNA (RNAi) begins when Dicer yields small interference RNA (siRNA) that bind to complementary mRNA for its degradation, forming the RISC complex. siRNA are naturally formed from transposons and dsRNA viruses during its replication, as well as from other bidirectional transcribed repetitive sequences. Some of the enzymes thar are part of the RNAi machinery, including Dicer, are encoded by multigene families in many species, that also play a role in other mechanisms of RND-dependent gene silencing. MicroRNA's (miRNA) are other small RNA's that can induce gene silencing at the mRNA level. These are formed in a general manner when Dicer process hairpin structures resulting from the transcription of non-coding sequences from plant and animal genomes. miRNA's are integrated into a RISC-like complex, after which, depending on their degree of complementarity with target mRNA, can either repress translation or induce mRNA degradation. miRNA-dependent silencing is essential for the development of multicellular organisms. Artificial RNAi induction by means of siRNA or miRNA is being used as a tool to inactivate gene expression in culture cells and in living organisms. This review focuses on the progress in the understanding of the mechanisms involved in gene regulation by RNA in animals and details some current efforts to apply theses phenomena as a tool in research and in the therapeutic of human diseases.

Humans↗

A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain.

microRNAs (or miRNAs) are small noncoding RNAs (21 to 25 nucleotides) that are processed from longer hairpin RNA precursors and are believed to be involved in a wide range of developmental and cellular processes, by either repressing translation or triggering mRNA degradation (RNA interference). By using a computer-assisted approach, we have identified 46 potential miRNA genes located in the human imprinted 14q32 domain, 40 of which are organized as a large cluster. Although some of these clustered miRNA genes appear to be encoded by a single-copy DNA sequence, most of them are arranged in tandem arrays of closely related sequences. In the mouse, this miRNA gene cluster is conserved at the homologous distal 12 region. In vivo all the miRNAs that we have detected are expressed in the developing embryo (both in the head and in the trunk) and in the placenta, whereas in the adult their expression is mainly restricted to the brain. We also show that the miRNA genes are only expressed from the maternally inherited chromosome and that their imprinted expression is regulated by an intergenic germline-derived differentially methylated region (IG-DMR) located approximately 200 kb upstream from the miRNA cluster. The functions of these miRNAs, which seem only conserved in mammals, are discussed both in terms of epigenetic control and gene regulation during development.

Animals↗

Co-expression of the Mammaglobin (SCGB2A2) Gene With hsa-miR-184 and hsa-miR-190b Indicates Its Possible Role in Oncogenic Pathways in Breast Cancer.

BACKGROUND/AIM: Breast cancer is the most common cancer in women worldwide, and early detection remains a significant challenge. Recent studies have identified increased expression of Mammaglobin A (Q13296, Gene: SCGB2A2) mRNA in breast cancer, suggesting its potential as a disease marker, although its function is not fully understood. To elucidate Mammaglobin's role, this study sought to identify co-expressed miRNAs and analyze the biological pathways they regulate. MATERIALS AND METHODS: Using TCGAbiolinks and Firebrowse, miRNA and gene expression data were collected from 86 patients, including tumor and normal tissue samples from the Cancer Genome Atlas (TCGA) Breast Cancer cohort. Transcriptomic data were analyzed with DESeq2, and a Spearman correlation was calculated for significant p-values, which were further explored using enrichment tools and target gene databases. RESULTS: DESeq2 was used to identify differential expression of miRNAs between normal and tumor breast tissues. Out of 782 miRNAs differentially expressed in breast cancer, hsa-mir-184 and hsa-mir-190b showed a significant positive correlation with SCGB2A expression. These markers were also upregulated in breast cancer tissues compared to normal tissues. Bioinformatics analysis revealed that hsa-mir-184 and hsa-mir-190b play important roles in cancer and cellular proliferation. These miRNAs target a wide range of genes, including sorting nexin 9 (SNX9) and annexin 6 (ANXA6), which are involved in membrane stability, vesicular trafficking, and cell mobility, and they contribute to cancer metastasis. CONCLUSION: The positive correlation among the expression of hsa-miR-184, hsa-miR-190b, and SCGB2A2 suggests that they may participate in shared biological pathways. These pathways govern critical cellular processes, such as membrane trafficking and cell signaling, which are frequently disrupted in cancer. Consequently, these findings enable a better understanding of the role of Mammaglobin in breast cancer signaling.

MicroRNAs (miRNAs)↗

A family of microRNAs present in plants and animals.

Although many miRNAs are deeply conserved within each kingdom, none are known to be conserved between plants and animals. We identified Arabidopsis thaliana miR854 and miR855, two microRNAs (miRNAs) with multiple binding sites in the 3' untranslated region (3'UTR) of OLIGOURIDYLATE binding PROTEIN1b (At UBP1b), forming miRNA:mRNA interactions similar to those that cause translational repression/mRNA cleavage in animals. At UBP1b encodes a member of a heterogeneous nuclear RNA binding protein (hnRNP) family. The 3'UTR of At UBP1b is sufficient to repress reporter protein expression in tissues expressing miR854 or miR855 (rosette leaves and flowers, respectively) but not where both miRNAs are absent (cauline leaves). Intergenic regions containing sequences closely resembling miR854 are predicted to fold into stable miRNA precursors in animals, and members of the miR854 family are expressed in Caenorhabditis elegans, Mus musculus, and Homo sapiens, all with imperfect binding sites in the 3'UTR of genes encoding the T cell Intracellular Antigen-Related protein, an hnRNP of the UBP1 family. Potential binding sites for miR854 are absent from UBP1-like genes in fungi lacking the miRNA biogenetic machinery. Our results indicate that plants and animals share miRNAs of the miR854 family, suggesting a common origin of these miRNAs as regulators of basal transcriptional mechanisms.

3' Untranslated Regions↗

Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences.

Drosha is a member of the ribonuclease (RNase) III family that selectively processes RNAs with prominent double-stranded features. Drosha plays a key role in the generation of precursor microRNAs from primary microRNA (pri-miRNA) transcripts in animal cells, yet how Drosha recognizes its RNA substrates remains incompletely understood. Previous studies have indicated that, within the context of a larger pri-miRNA, an approximately 80-nucleotide-long RNA hairpin structure is necessary for processing by Drosha. Here, by performing in vitro Drosha processing reactions with RNA substrates of various sizes and structures, we show that Drosha function also requires single-stranded RNA extensions located outside the pri-miRNA hairpin. The sequence of these RNA extensions was largely unimportant, but a strong secondary structure within the extension or a blunt-ended pri-miRNA hairpin blocked Drosha cleavage. The requirement for single-stranded extensions on the pri-miRNA hairpin substrate for Drosha processing is currently unique among the RNase III enzymes.

Base Sequence↗

Repression of protein synthesis by miRNAs: how many mechanisms?

MicroRNAs are approximately 21-nucleotide-long regulators of gene expression that gain access to their target mRNAs by complementary base pairing. Recent studies have revealed that animal microRNAs might take diverse routes to repress gene expression, affecting both target mRNA levels and translation. Mechanistic details of microRNA-mediated repression are starting to emerge but a comprehensive picture of the inhibition, and particularly the effects on mRNA translation, is still lacking. Recent data support different microRNA mechanisms and a role for cytoplasmic processing bodies in the degradation and storage of mRNAs targeted by microRNA regulators.

Animals↗

Computational prediction of microRNAs encoded in viral and other genomes.

We present an overview of selected computational methods for microRNA prediction. It is especially aimed at viral miRNA detection. As the number of microRNAs increases and the range of genomes encoding miRNAs expands, it seems that these small regulators have a more important role than has been previously thought. Most microRNAs have been detected by cloning and Northern blotting, but experimental methods are biased towards abundant microRNAs as well as being time-consuming. Computational detection methods must therefore be refined to serve as a faster, better, and more affordable method for microRNA detection. We also present data from a small study investigating the problems of computational miRNA prediction. Our findings suggest that the prediction of microRNA precursor candidates is fairly easy, while excluding false positives as well as exact prediction of the mature microRNA is hard. Finally, we discuss possible improvements to computational microRNA detection.

Journal Article↗

Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.

RNA interference is implemented through the action of the RNA-induced silencing complex (RISC). Although Argonaute2 has been identified as the catalytic center of RISC, the RISC polypeptide composition and assembly using short interfering RNA (siRNA) duplexes has remained elusive. Here we show that RISC is composed of Dicer, the double-stranded RNA binding protein TRBP, and Argonaute2. We demonstrate that this complex can cleave target RNA using precursor microRNA (pre-miRNA) hairpin as the source of siRNA. Although RISC can also utilize duplex siRNA, it displays a nearly 10-fold greater activity using the pre-miRNA Dicer substrate. RISC distinguishes the guide strand of the siRNA from the passenger strand and specifically incorporates the guide strand. Importantly, ATP is not required for miRNA processing, RISC assembly, or multiple rounds of target-RNA cleavage. These results define the composition of RISC and demonstrate that miRNA processing and target-RNA cleavage are coupled.

Adenosine Triphosphate↗

Nuclear processing and export of microRNAs in Arabidopsis.

In mammalian cells, the nuclear export receptor, Exportin 5 (Exp5), exports pre-microRNAs (pre-miRNAs) as well as tRNAs into the cytoplasm. In this study, we examined the function of HASTY (HST), the Arabidopsis ortholog of Exp5, in the biogenesis of miRNAs and tRNAs. In contrast to mammals, we found that miRNAs exist as single-stranded 20- to 21-nt molecules in the nucleus in Arabidopsis. This observation is consistent with previous studies indicating that proteins involved in miRNA biogenesis are located in the nucleus in Arabidopsis. Although miRNAs exist in the nucleus, a majority accumulate in the cytoplasm. Interestingly, loss-of-function mutations in HST reduced the accumulation of most miRNAs but had no effect on the accumulation of tRNAs and endogenous small interfering RNAs, or on transgene silencing. In contrast, a mutation in PAUSED (PSD), the Arabidopsis ortholog of the tRNA export receptor, Exportin-t, interfered with the processing of tRNA-Tyr but did not affect the accumulation or nuclear export of miRNAs. These results demonstrate that HST and PSD do not share RNA cargos in nuclear export and strongly suggest that there are multiple nuclear export pathways for these small RNAs in Arabidopsis.

Active Transport, Cell Nucleus↗

iMSC-derived extracellular vesicles and their miRNA cargo influence inflammation and oxidative damage in an in vitro osteoarthritis model.

Osteoarthritis is a multifactorial chronic joint disease characterized by progressive cartilage degradation and inflammation. Since there is no effective cure, emerging therapeutic approaches, such as mesenchymal stromal cells (MSCs) transplantation, are currently under investigation. However, the clinical translation of MSC-based therapies is hampered by several limitations, such as donor-dependent variability and heterogeneity related to tissue sources. To address these issues, MSCs derived from induced pluripotent stem cells (iMSCs) have been proposed as a more standardized and scalable alternative. Due to the risks of cell-based therapy, extracellular vesicles (EVs), particularly iMSC-EVs (iEVs), could represent a promising cell-free approach for OA treatment. The present study aimed at characterizing iMSC-derived EVs and evaluating their functional role in modulating inflammatory responses and redox balance in an in vitro OA model. Notably, recent evidence highlights the central role of EV-encapsulated microRNAs (EV-miRNAs) in mediating these effects. EVs isolated from iMSC conditioned media were characterized, and their miRNA content was analyzed at different culture passages. Selected miRNAs were subsequently assessed for their biological activity in an in vitro OA model, with a focus on their impact on inflammatory mediators and oxidative stress parameters. Specifically, six miRNAs such as hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p differentially reflect the anti-inflammatory and antioxidant effects of iMSCs-EVs treatment, suggesting possible synergistic effects. Their combined effect in the in vitro model confirmed their potential modulation in the expression of pro-inflammatory cytokines. Furthermore, their treatment markedly reduced ROS accumulation and oxidative damage, while restoring antioxidant defense systems. These findings support the therapeutic potential of iMSC-derived EVs as a cell-free strategy for OA treatment. The miRNA cargo encapsulated within iEVs appears to play a pivotal role in modulating inflammation and oxidative stress, emphasizing their promise as a novel, minimally invasive approach for disease modification in OA.

MicroRNAs↗

An Exosomal Signature for Preoperative Detection of Occult Liver Metastasis in Pancreatic Cancer.

IMPORTANCE: Early liver metastasis (early-LiM) after pancreatectomy represents an aggressive biological phenotype of pancreatic ductal adenocarcinoma (PDAC) and is associated with markedly poor survival. Reliable preoperative biomarkers to identify occult hepatic micrometastasis remain lacking. OBJECTIVE: To develop and externally validate a circulating exosomal microRNA (exo-miRNA)-based machine learning model for preoperative detection of occult early-LiM in PDAC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case-control study included 3 phases: genome-wide discovery using exo-miRNA sequencing (discovery cohort), model development (training cohort), and independent external validation (2 validation cohorts). The study took place at 4 medical centers in China, Japan, and South Korea. A total of 372 patients were enrolled between 2011 and 2024. Data were analyzed from July 2024 to November 2025. EXPOSURES: Circulating plasma-derived exosomal miRNA expression profiles. MAIN OUTCOMES AND MEASURES: The primary outcome was early-LiM, defined as liver recurrence within 6 months after curative-intent resection. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and survival outcomes were assessed using Kaplan-Meier analysis. RESULTS: Among 372 patients with PDAC (median [IQR] age, 67 [59-73] years; 229 [61.6%] male and 143 [38.4%] female; median follow-up among survivors, 969 days),early-LiM was associated with significantly worse overall survival compared with other recurrence patterns (median OS, 9.1 months vs 26.6-31.8 months; log-rank P&#x2009;<&#x2009;.001). A 7-exo-miRNA extreme gradient boosting model demonstrated discrimination in the training cohort (AUC, 0.899; 95% CI, 0.822-0.976) and maintained performance in external testing cohorts (AUC, 0.876; 95% CI, 0.846-0.951 and AUC, 0.862; 95% CI, 0.744-0.981). The exo-miRNA panel score remained an independent identifier of early-LiM in multivariable analysis (odds ratio, 26.49; 95% CI, 18.45-55.28; P&#x2009;<&#x2009;.001) and stratified overall survival (log-rank P&#x2009;<&#x2009;.001). Decision curve analysis suggested improved net clinical benefit compared with conventional clinicopathologic variables. CONCLUSION AND RELEVANCE: In this multicenter study, a circulating exo-miRNA-based machine learning model enabled preoperative detection of occult early liver metastasis risk in PDAC. These findings support the potential of exosomal biomarkers to inform biology-guided treatment sequencing and warrant prospective validation.

Journal Article↗

Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing.

DGCR8/Pasha is an essential cofactor for Drosha, a nuclear RNase III that cleaves the local hairpin structures embedded in long primary microRNA transcripts (pri-miRNAs) in eukaryotes. Although our knowledge of pri-miRNA processing has significantly advanced in recent years, the precise role of DGCR8 in this pathway remains unclear. In our present study, we dissect the domains in DGCR8 that contribute to the processing of pri-miRNAs and the subcellular localization of DGCR8. Drosha is stabilized through an interaction between its middle domain and the conserved C-terminal domain of DGCR8. Furthermore, DGCR8, but not Drosha, can directly and stably interact with pri-miRNAs, and the tandem dsRNA-binding domains (dsRBDs) in DGCR8 are responsible for this recognition. Moreover, the DGCR8 N-terminal region upstream of its dsRBDs is unnecessary for pri-miRNA processing but is critical for nuclear localization. Our study thus provides further insights into the mechanism of action of the Drosha-DGCR8 complex in pri-miRNA processing.

Amino Acid Sequence↗

Drosha versus ADAR: wrangling over pri-miRNA.

Processing of a mammalian hematopoietic microRNA precursor is suppressed when it is edited by ADARs. The edited pri-miRNA can subsequently be degraded by Tudor-SN.

Adenosine Deaminase↗

Phylogenetic shadowing and computational identification of human microRNA genes.

We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in conservation was found for sequences immediately flanking the miRNA hairpins. This characteristic profile was employed to predict novel miRNAs using cross-species comparisons. Nine hundred and seventy-six candidate miRNAs were identified by scanning whole-genome human/mouse and human/rat alignments. Most of the novel candidates are conserved also in other vertebrates (dog, cow, chicken, opossum, zebrafish). Northern blot analysis confirmed the expression of mature miRNAs for 16 out of 69 representative candidates. Additional support for the expression of 179 novel candidates can be found in public databases, their presence in gene clusters, and literature that appeared after these predictions were made. Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated.

Computational Biology↗

Multiplexing RT-PCR for the detection of multiple miRNA species in small samples.

MicroRNAs are short (approximately 22 nucleotides), non-coding RNAs that play critical roles in gene regulation and may be used as rapid precise diagnostic indicators of early stages of cancer. The small size of these RNAs makes detection of multiple microRNA species in very small samples problematic. Here we investigate the parameters associated with multiplexing RT-PCR to obtain relative abundance profiles of multiple microRNAs in small sample sizes down to the amount of RNA found in a single cell.

Humans↗