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Results for “MicroRNA”

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At least 271 records · Page 15Linked to original sources

PubMed2005

Hematopoietic-specific microRNA expression in human cells.

We examined expression profiles of hematopoietic tissue-specific microRNAs (miRNAs; miR-142, miR-155, miR-181 and miR-223) in 17 commercially available malignant hematopoietic cell lines and compared to those in highly purified normal human B, T, monocytic and granulocytic lineages. Although malignant cell lines examined showed miRNA expression patterns similar to normal human hematopoietic lineages, the levels of miRNA expression among cell lines and normal cell lineages were considerably different, indicating the significance of miRNAs in human hematopoietic diseases. Further our results showed differences in miRNA expression between mouse and human hematopoietic cells, suggesting important regulatory roles of miRNAs in human hematopoiesis and oncogenesis.

Animals↗

PubMed2005

MicroRNA modulation of megakaryoblast fate involves cholinergic signaling.

MicroRNAs (miRNAs) are abundant small regulatory RNAs with multiple roles in cell fate determination. The processes regulating cellular miRNA levels are still unclear and experimental oligonucleotide tools to readily mimic their effects are not yet available. Here, we report that thapsigargin-induced intracellular Ca(++) release suppressed pre-miR-181a levels in human promegakaryotic Meg-01 cells, induced differentiation-associated nuclear endoreduplication and caspase-3 activation and replaced the acetylcholinesterase 3' splice variant AChE-S with AChE-R. AChE, PKC and PKA inhibitors all attenuated the pre-miR-181a decline and the induced differentiation. AChmiON, a synthetic 23-mer 2'-oxymethylated oligonucleotide mimicking the miR-181a sequence, blocked the calcium-induced differentiation while elevating cellular pre-miR-181a levels and inducing DNA fragmentation and cell death. Moreover, when added to RW 264.7 macrophages, AChmiON at 100 nM induced nitric oxide production with efficiency close to that of bacterial endotoxin, demonstrating physiologically relevant activities also in blood-born monocytes/macrophages. The stress-induced modulation of hematopoietic miR-181a levels through AChE, PKC and PKA cascade(s) suggests using miRNA mimics for diverting the fate of hematopoietic tumor cells towards differentiation and/or apoptosis.

Acetylcholinesterase↗

PubMed2006

Nonisotopic detection of microRNA using digoxigenin labeled RNA probes.

MicroRNAs (miRNAs) are an important class of endogenously derived, small approximately 22 nucleotide noncoding regulatory RNAs that have recently become implicated in development, cell regulation and cancers of various tissues. Here we report a nonisotopic Northern analysis method for miRNA detection using 3'-digoxigenin (DIG)-labeled RNA oligo probes. Northern blot analysis was performed using miRNA or total RNA fractions extracted from human leukemic cell lines, and blots were hybridized with either 32P- or DIG-labeled RNA probe for miR-181, miR-155 or miR-16. A labeled probe for U6 small nuclear RNA served as an internal control. The use of DIG-labeled RNA probes was equally sensitive compared to 32P-labeled probes in detecting miRNA quantities as low as 50 ng. The ability to use nonisotopic methods and yet obtain sensitive and reliable results offers an advantage to investigators who prefer to avoid isotopes.

Blotting, Northern↗

PubMed2006

The adaptation of TSH secretion to autonomy in non-toxic goiter may be based-on active regulation of set-point and sensitivity of central TSH-receptors, perhaps by the microRNA (MIR) gene.

The hypothalamic-pituitary-thyroid (HPT) feedback system is one of the most complex regulatory systems and it has intrigued researchers for more than 50 years. One of the unsolved problems of this regulation in humans is the hypothalamic and pituitary adaption to autonomous function of the thyroid gland in non-toxic goiter (NTG). A new hypothesis, that TSH secretion is actively regulated in NTG in response to changes in thyroid autonomy in order to keep the patient euthyroid, was discussed in the present study on basis of previous experimental data in NTG patients with different degree of autonomous function. The patients were submaximally suppressed for one month with a fixed daily dose of T3. Group data suggested an inverse correlation between TSH suppression and suppression of thyroid function. Group data also suggested that TSH suppression was significantly correlated to basal TSH. This means that a NTG patient with a low normal TSH in blood before suppression (basal TSH) and a high degree of autonomous function may exhibit a relatively high TSH suppression. This ensures a minimal stimulation of the thyroid gland thereby protecting the gland from developing hyperthyroidism. A patient with a high normal TSH in blood before suppression (basal TSH) and a low degree of autonomous function, may exhibit a relatively low TSH suppression, indicating a high stimulation of the thyroid gland thereby protecting the patient from developing hypothyroidism. It is hypothesized that this adaption of TSH secretion to autonomy in NTG patients may be based on active regulation of both the set- point of the central TSH-receptors and the sensitivity of these receptors as well. Such an active regulation of the HPT axis may be controlled by one of the newly found post-transcriptional genes called MIR (microRNA).

Adaptation, Physiological↗

PubMed2004

Computational identification of plant microRNAs and their targets, including a stress-induced miRNA.

MicroRNAs (miRNAs) are approximately 21-nucleotide RNAs, some of which have been shown to play important gene-regulatory roles during plant development. We developed comparative genomic approaches to systematically identify both miRNAs and their targets that are conserved in Arabidopsis thaliana and rice (Oryza sativa). Twenty-three miRNA candidates, representing seven newly identified gene families, were experimentally validated in Arabidopsis, bringing the total number of reported miRNA genes to 92, representing 22 families. Nineteen newly identified target candidates were confirmed by detecting mRNA fragments diagnostic of miRNA-directed cleavage in plants. Overall, plant miRNAs have a strong propensity to target genes controlling development, particularly those of transcription factors and F-box proteins. However, plant miRNAs have conserved regulatory functions extending beyond development, in that they also target superoxide dismutases, laccases, and ATP sulfurylases. The expression of miR395, the sulfurylase-targeting miRNA, increases upon sulfate starvation, showing that miRNAs can be induced by environmental stress.

Arabidopsis↗

PubMed2005

MicroRNAs and viral infection.

MicroRNAs (miRNAs) play a pivotal role in the regulation of genes involved in diverse processes such as development, differentiation, and cellular growth control. Recently, many viral-encoded miRNAs have been discovered, for the most part in viruses transcribed from double-stranded DNA genomes. As with their cellular counterparts, the functions of most viral-derived miRNAs are unknown; however, functions have been documented or proposed for viral miRNAs from three different viral families-herpesviruses, polyomaviruses, and retroviruses. Several virus-encoded miRNAs have unique aspects to their biogenesis, such as the polymerase that transcribes them or their location within the precursor transcript. Additionally, viral interactions with cellular miRNAs have also been identified, and these have substantially expanded our appreciation of miRNA functions.

Animals↗

PubMed2006

MicroRNA pathways modulate polyglutamine-induced neurodegeneration.

Nine human neurodegenerative diseases are due to expansion of a CAG repeat- encoding glutamine within the open reading frame of the respective genes. Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell death during development. To address whether miRNA pathways play a role in neurodegeneration, we tested whether genes critical for miRNA processing modulated toxicity induced by the spinocerebellar ataxia type 3 (SCA3) protein. These studies revealed a striking enhancement of polyQ toxicity upon reduction of miRNA processing in Drosophila and human cells. In parallel genetic screens, we identified the miRNA bantam (ban) as a potent modulator of both polyQ and tau toxicity in flies. Our studies suggest that ban functions downstream of toxicity of the SCA3 protein, to prevent degeneration. These findings indicate that miRNA pathways dramatically modulate polyQ- and tau-induced neurodegeneration, providing the foundation for new insight into therapeutics.

Animals↗

PubMed2006

MicroRNA therapeutics: a new niche for antisense nucleic acids.

MicroRNA molecules (miRNAs) are naturally occurring triggers of the RNA-interference pathway. The first identified miRNA, lin-4, was discovered in Caenorhabditis elegans >20 years ago. What began as a curiosity in this model organism has expanded into almost every area of biology; there are now 326 confirmed miRNA genes in humans and the total is predicted to reach 1000. Each miRNA has the potential to regulate hundreds of mRNAs; therefore, there are likely to be few biological pathways not impacted by miRNA regulation. Recent evidence has suggested that miRNAs might be viable therapeutic targets for a wide range of diseases, including cancer. A recent article by Stoffel and colleagues has demonstrated remarkably effective inhibition of miRNAs in vivo, thus providing an entry point into the promising new arena of miRNA therapeutics.

Animals↗

PubMed2006

MicroRNA expression and function in cancer.

MicroRNAs are small non-coding RNAs of 19-24 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Large high-throughput studies in patients revealed that miRNA profiling have the potential to classify tumors with high accuracy and predict outcome. Functional studies, some of which involve animal models, indicate that miRNAs act as tumor suppressors and oncogenes. Here, we summarize miRNA-profiling studies in human malignancies and examine the role of miRNAs in the pathogenesis of cancer. We also discuss the implications of these findings for the diagnosis and treatment of cancer.

Animals↗

PubMed2005

Stem cells: from epigenetics to microRNAs.

The complexity and cellular diversity of the adult brain arises from the proliferation and differentiation of a small number of stem cells. The intrinsic state of stem cells depends on their spatial and temporal history and affects their responsiveness to extrinsic signals from the microenvironment. Stem cell self-renewal and differentiation along neuronal and glial lineages are defined by the dynamic interplay between transcription, epigenetic control, and posttranscriptional regulators, including microRNAs, whose key role in stem cell biology is just emerging.

Animals↗

PubMed2004

MicroRNAs: something important between the genes.

Non-coding small endogenous RNAs, of 21-24 nucleotides in length, have recently emerged as important regulators of gene expression in both plants and animals. At least three categories of small RNAs exist in plants: short interfering RNAs (siRNAs) deriving from viruses or transgenes and mediating virus resistance or transgene silencing via RNA degradation; siRNAs deriving from transposons or transgene promoters and controlling transposon and transgene silencing probably via chromatin changes; and microRNAs (miRNAs) deriving from intergenic regions of the genome and regulating the expression of endogenous genes either by mRNA cleavage or translational repression. The disruption of miRNA-mediated regulation causes developmental abnormalities in plants, demonstrating that miRNAs play an important role in the regulation of developmental decisions.

Gene Expression Regulation, Plant↗

PubMed2005

The developmental role of microRNA in plants.

MicroRNAs (miRNAs) are single-stranded RNA molecules of around 22 nucleotides (nt) in length that are associated with the RNA-induced silencing complex (RISC). They play an important role in plant development, either by targeting mRNA for cleavage or by inhibiting translation. Over the past year, the list of known miRNAs, confirmed targets and developmental effects has expanded, as has the realization that they are conserved during evolution and that small RNAs can play a direct role in cell-cell signaling.

Gene Expression Regulation, Developmental↗

PubMed2026

Comparative analysis of DDR-related genes and microRNA expression during rice germination: Implications for salinity susceptibility screening.

Soil salinity poses a significant threat to the agri-food sector and particularly to rice cultivation. High salinity during germination induces overproduction of reactive oxygen species (ROS) that cause lesions in the DNA resulting in reduced vigor. MicroRNAs (miRNAs) are known to modulate stress response in plants, however, studies focusing on its relation with the expression of the DNA damage response (DDR)-related genes are not thoroughly explored. In this regard, the aim of this work was to investigate the link between the expression of miRNAs and putative targeted DDR-related genes in response to salinity stress during germination. Eight varieties representative of indica and japonica rice subspecies were categorized into clusters through a principal component analysis (PCA) based on their germination performance and stress tolerance index under varying concentrations of NaCl. Subsequently, the expression patterns of six miRNAs and their putative targeted DDR genes were measured in two contrastive cultivars through quantitative real-time PCR (qRT-PCR) while correlations were examined through Pearson's analysis. Results showed distinct expression profiles between halotolerant and sensitive cultivars. Two miRNAs were further investigated in mature dry seeds of all the cultivars to verify their earliest, seed-specific discriminative potential. The distinct miR414 expression pattern may represent a potential biomarker for identifying salinity-susceptible cultivars during early-stage breeding screening.

Oryza↗

PubMed2005

MicroRNAs as regulators of mammalian hematopoiesis.

MicroRNAs (miRNAs) are an abundant class of approximately 22 nucleotide non-coding RNAs and play important regulatory roles in animal and plant development at the post-transcriptional level. Many miRNAs cloned from mouse bone marrow cells are differentially regulated in various hematopoietic lineages, suggesting that they might influence hematopoietic lineage differentiation. miR-181, a miRNA specifically expressed in B cells within mouse bone marrow, promotes B-cell differentiation when expressed in hematopoietic stem/progenitor cells. Some human miRNAs are linked to leukemias: the miR-15a/miR-16 locus is frequently deleted or down-regulated in patients with B-cell chronic lymphocytic leukemia and miR-142 is at a translocation site found in a case of aggressive B-cell leukemia. Collectively, these results indicate that miRNAs may be important regulators of mammalian hematopoiesis. Here, we provide background on the biogenesis and function of miRNAs and discuss how miRNA-mediated post-transcriptional regulation may influence the development and function of blood cells.

Animals↗

PubMed2004

Common logic of transcription factor and microRNA action.

Over the past few years, microRNAs (miRNAs) have emerged as abundant regulators of gene expression. Like many transcription factors (TFs), miRNAs are important determinants of cellular fate specification. Here I provide a conceptual framework for miRNA action in the context of creating cellular diversity in a developing organism, and emphasize the conceptual similarity of TF- and miRNA-mediated control of gene expression. Both TFs and miRNAs are trans-acting factors that exert their activity through composite cis-regulatory elements that are 'hard-wired' into DNA or RNA. TFs and miRNAs act in a largely combinatorial manner - that is, many different TFs or miRNAs control one gene - and they act cooperatively on their targets - that is, there are several cis-regulatory elements for a single TF or miRNA species in a target gene. Just as the set of TFs in a given cell type has been proposed to constitute a 'code' that specifies cellular differentiation, so 'miRNA codes' are likely to have conceptually similar roles in the specification of cell types.

Animals↗

PubMed2006

Genomics of microRNA.

Discovered just over a decade ago, microRNA (miRNA) is now recognized as one of the major regulatory gene families in eukaryotic cells. Hundreds of miRNAs have been found in animals, plants and viruses, and there are certainly more to come. Through specific base-pairing with mRNAs, these tiny approximately 22-nt RNAs induce mRNA degradation or translational repression, or both. Because a miRNA can target numerous mRNAs, often in combination with other miRNAs, miRNAs operate highly complex regulatory networks. In this article, we summarize the current status of miRNA gene mining and miRNA expression profiling. We also review up-to-date knowledge of miRNA gene structure and the biogenesis mechanism. Our focus is on animal miRNAs.

Animals↗

PubMed2006

Virus-encoded microRNAs: novel regulators of gene expression.

MicroRNAs (miRNAs) are a class of small RNAs that have recently been recognized as major regulators of gene expression. They influence diverse cellular processes ranging from cellular differentiation, proliferation, apoptosis and metabolism to cancer. Bioinformatic approaches and direct cloning methods have identified >3500 miRNAs, including orthologues from various species. Experiments to identify the targets and potential functions of miRNAs in various species are continuing but the recent discovery of virus-encoded miRNAs indicates that viruses also use this fundamental mode of gene regulation. Virus-encoded miRNAs seem to evolve rapidly and regulate both the viral life cycle and the interaction between viruses and their hosts.

Animals↗

PubMed2004

Derivation and function of small interfering RNAs and microRNAs.

Small interfering RNA (siRNA) duplexes are generally produced by Dicer cleavage of double-stranded RNAs of frequently exogenous origin and can induce the cleavage and degradation of mRNAs bearing an identical sequence. In contrast, microRNAs (miRNAs) are encoded within the eukaryotic genome as short RNA hairpin structures. While these pre-miRNAs are also processed by Dicer, mature miRNAs appear to function primarily by inhibiting the translation of mRNAs bearing multiple, partially mismatched target sites. Nevertheless, recent data argue that the posttranscriptional regulatory machinery utilized by siRNAs and miRNAs is largely or entirely identical. In this review, I will discuss recent progress in unraveling the RNA processing pathway utilized for the biosynthesis of mature miRNAs and argue that this pathway offers at least three distinct entry points for the functional expression of artificial siRNAs in vertebrate cells. While each of these entry points offers distinct advantages and disadvantages, they all have the potential to induce the effective knock-down of specific genes either in cell culture or in experimental animals.

MicroRNAs↗