Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging.

ABSTRACT: Aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. To better understand the genetic component of aging, many studies have addressed the gene and protein expression profiles of various aging model systems engaging different organisms from yeast to human. The recently identified small non-coding miRNAs are potent post-transcriptional regulators that can modify the expression of up to several hundred target genes per single miRNA, similar to transcription factors. Increasing evidence shows that miRNAs contribute to the regulation of most if not all important physiological processes, including aging. However, so far the contribution of miRNAs to age-related and senescence-related changes in gene expression remains elusive. To address this question, we have selected four replicative cell aging models including endothelial cells, replicated CD8(+) T cells, renal proximal tubular epithelial cells, and skin fibroblasts. Further included were three organismal aging models including foreskin, mesenchymal stem cells, and CD8(+) T cell populations from old and young donors. Using locked nucleic acid-based miRNA microarrays, we identified four commonly regulated miRNAs, miR-17 down-regulated in all seven; miR-19b and miR-20a, down-regulated in six models; and miR-106a down-regulated in five models. Decrease in these miRNAs correlated with increased transcript levels of some established target genes, especially the cdk inhibitor p21/CDKN1A. These results establish miRNAs as novel markers of cell aging in humans.

SUBMITTER: Hackl M

PROVIDER: S-EPMC2848978 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated by miR-17 and miR-20a.

Project description:FBXO31, a subunit of the SCF ubiquitin ligase, played a crucial role in neuronal development, DNA damage response and tumorigenesis. Here, we investigated the expression and prognosis value of FBXO31 in human primary gastric cancer (GC) samples. Meanwhile, the biological role and the regulation mechanism of FBXO31 were evaluated. We found that FBXO31 mRNA and protein was decreased dramatically in the GC tissue compared with the adjacent non-cancerous tissues. FBXO31 expression was significantly associated with tumor size, tumor infiltration, clinical grade and patients' prognosis. FBXO31 overexpression significantly decreased colony formation and induced a G1-phase arrest and inhibited the expression of CyclinD1 protein in GC cells. Further evidence was obtained from knockdown of FBXO31. Ectopic expression of FBXO31 dramatically inhibited xenograft tumor growth in nude mice. miR-20a and miR-17 mimics inhibited, whereas the inhibitor of miR-20a and miR-17 increased, the expression of FBXO31, respectively. miR-20a and miR-17 directly bind to the 3'-UTR of FBXO31. The level of miR-20a and miR-17 in GC tissue was significantly higher than that in surrounding normal mucosa. Moreover, a highly significant negative correlation between miR-20a (miR-17) and FBXO31 was observed in these GC samples. Therefore, effective therapy targeting the miR-20a (miR-17)-FBXO31-CyclinD1 pathway may help control GC progression.

| S-EPMC4171621 | biostudies-literature

MicroRNA profiling of human dermal fibroblasts - miR-17 and miR-19b to investigate down-regulatation in human aging

Project description:Normal human fibroblasts were isolated from skin biopsies of two different healthy causcasian patients, a 41-years old female (HDF-1) and a 16-years old male (HDF-5). HDF-5 and HDF-1 cells were cultivated in DMEM/HAMs F-12 medium (Biochrom KG, Berlin, Germany) supplemented with 10% fetal calf serum (FCS) 4 mM L-glutamine (Sigma) and Primocin antibiotics (100 µg/mL) grown at 37 °C in ambient atmosphere containing 5% CO2. Cells were grown until confluence was reached and routinely passaged using 1:4 or 1:3 split ratios. Upon decrease in growth rate and entry of irreversible growth arrest split ratio was changed to 1:2 until cells stopped dividing and fresh medium was added at least every 7 days. HDF-1 cells reached senescence after 54 population doublings, while HDF-5 cells had stopped growing after 72.7 population doublings (see Fig. S2 for growth curves and staining of senescent associated beta-galactosidase).<br>Senescent HDF RNA samples were compared to young HDF RNA samples in terms of microRNA expression using Exiqon LNA microRNA microarrays.

2010-04-19 | E-MEXP-2386 | biostudies-arrayexpress

MicroRNA profiling of human CD8 T cells - miR-17 and miR-19b to investigate down-regulatation in human aging

Project description:T cells from several blood donors were separated in populations corresponding to CD8+ CD28+ and CD8+ CD28- surface markers. Total RNA extracts from cells were hybridized to MRC LNA microarray. Contrasts of interest were CD8CD28- minus CD8CD28+ (replicative aging) and CD8CD28+ (old donors) minus CD8CD28+ (young donors), which corresponds to chronological aging.

2010-04-19 | E-MEXP-2398 | biostudies-arrayexpress

The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation.

Project description:Mononuclear cytotrophoblasts of the human placenta proliferate rapidly, subsequently fuse, and differentiate to form multinucleated syncytiotrophoblast with induction of aromatase (hCYP19A1) and chorionic gonadotropin (hCG?) expression. Using microarray analysis, we identified members of the miR-17~92 cluster and its paralogs, miR-106a~363 and miR-106b~25, that are significantly downregulated upon syncytiotrophoblast differentiation. Interestingly, miR-19b and miR-106a directly targeted hCYP19A1 expression, while miR-19b also targeted human GCM1 (hGCM1), a transcription factor critical for mouse labyrinthine trophoblast development. Overexpression of these microRNAs (miRNAs) impaired syncytiotrophoblast differentiation. hGCM1 knockdown decreased hCYP19A1 and hCG? expression, substantiating its important role in human trophoblast differentiation. Expression of the c-Myc proto-oncogene was increased in proliferating cytotrophoblasts compared to that in differentiated syncytiotrophoblast. Moreover, c-Myc overexpression upregulated miR-17~92 and inhibited hCYP19A1 and hCG? expression. Binding of endogenous c-Myc to genomic regions upstream of the miR-17~92 and miR-106a~363 clusters in cytotrophoblasts dramatically decreased upon syncytiotrophoblast differentiation. Intriguingly, we observed higher levels of miR-106a and -19b and lower aromatase and hGCM1 expression in placentas from preeclamptic women than in placentas from gestation-matched normotensive women. Our findings reveal that c-Myc-regulated members of the miR-17~92 and miR-106a~363 clusters inhibit trophoblast differentiation by repressing hGCM1 and hCYP19A1 and suggest that aberrant regulation of these miRNAs may contribute to the pathogenesis of preeclampsia.

| S-EPMC3624183 | biostudies-literature

MicroRNA-17/20a/106a modulate macrophage inflammatory responses through targeting signal-regulatory protein ?.

Project description:BACKGROUND:Signal-regulatory protein ? (SIRP?) is an essential signaling molecule that modulates leukocyte inflammatory responses. However, the regulation of selective SIRP? synthesis and its dynamic changes in leukocytes under inflammatory stimulation remain incompletely understood. OBJECTIVE:We sought to identify the microRNAs (miRNAs) that posttranscriptionally regulate SIRP? synthesis and their roles in modulating macrophage inflammatory responses. METHODS:SIRP? was induced in SIRP?-negative promyelocytic cells by retinoic acid or phorbol 12-myristate 13-acetate, and the differential expression of miRNAs was assessed by means of microarray and quantitative RT-PCR assays. The roles of identified miRNAs in controlling SIRP? synthesis in leukocytes and leukocyte inflammatory responses were determined. RESULTS:We identified SIRP? as a common target gene of miR-17, miR-20a, and miR-106a. During SIRP? induction, levels of these 3 miRNAs were all reduced, and their downregulation by retinoic acid or phorbol 12-myristate 13-acetate occurred through suppression of the c-Myc signaling pathway. All miR-17, miR-20a, and miR-106a specifically bound to the same seed sequence within the SIRP? 3' untranslated region and correlated inversely with SIRP? protein levels in various cells. In macrophages upregulation of miR-17, miR-20a, and miR-106a by LPS served as the mechanism underlying LPS-induced SIRP? reduction and macrophage activation. Both in vitro and in vivo assays demonstrate that miR-17, miR-20a, and miR-106a regulate macrophage infiltration, phagocytosis, and proinflammatory cytokine secretion through targeting SIRP?. CONCLUSION:These findings demonstrate for the first time that miR-17, miR-20a, and miR-106a regulate SIRP? synthesis and SIRP?-mediated macrophage inflammatory responses in a redundant fashion, providing a novel pathway in which a panel of miRNAs can modulate immune polarization through regulation of macrophage activation.

| S-EPMC5882493 | biostudies-literature

MicroRNA profiling of human renal tubular epithelial cells - miR-17 and miR-19b to investigate their down-regulatation in human aging

Project description:Renal Tubular Epithelial Cells (RPTEC) from two donors were cultivated in vitro until irreversible growth arrest was observed. Total RNA from young (replicating) as well as growth arrested cells was harvested and hybridized to LNA based microRNA microarrays using a looped design. After data processing, differential expression of miRNAs in senescent vs. young RPTEC cells was calculated.

2010-04-19 | E-MEXP-2393 | biostudies-arrayexpress

miR-17-5p and miR-19b-3p prevent osteoarthritis progression by targeting EZH2.

Project description:Osteoarthritis (OA) is a joint disease caused by a variety of factors, including aging, obesity and trauma. MicroRNAs (miRNAs) have been reported to be crucial regulators during OA progression. The present study aimed to investigate the role of miR-17-5p and miR-19b-3p during OA development. Interleukin (IL)-1?-treated chondrocytes were used to mimic OA in vitro. The expression levels of miR-17-5p and enhancer of zeste homolog 2 (EZH2) were measured in cartilage tissues and chondrocytes using reverse transcription-quantitative PCR or western blotting. Apoptosis was assessed by flow cytometry. The protein expression levels of extracellular matrix (ECM)-associated genes were detected by western blotting. The binding sites between miR-17-5p or miR-19b-3p and EZH2 were predicted using the MicroT-CDS online database and verified using dual-luciferase reporter and RIP assays. miR-17-5p expression was downregulated, whereas EZH2 expression was upregulated in OA cartilage tissues and IL-1?-induced chondrocytes compared with that in the control tissues and cells. miR-17-5p mimics inhibited IL-1?-induced apoptosis and ECM degradation in chondrocytes. EZH2 was the target of miR-17-5p and miR-19b-3p in chondrocytes, and enhanced apoptosis and ECM degradation in IL-1?-stimulated chondrocytes. Rescue experiments revealed that miR-17-5p or miR-19b-3p mimic-induced inhibition of OA progression was reversed by EZH2 overexpression. In conclusion, miR-17-5p and miR-19b-3p inhibited OA progression by targeting EZH2, which may serve as a potential therapeutic target for OA.

| S-EPMC7388554 | biostudies-literature

SRSF3 shapes the structure of miR-17-92 cluster RNA and promotes selective processing of miR-17 and miR-20a

Project description:MicroRNA (miRNA) biogenesis is tightly regulated to maintain distinct miRNA expression patterns. Almost half of mammalian miRNAs are generated from miRNA clusters, but this process is not well understood. We show here that Serine-arginine rich splicing factor 3 (SRSF3) controls the processing of miR-17-92 cluster miRNAs in pluripotent and cancer cells. SRSF3 binding to multiple CNNC motifs downstream of Drosha cleavage sites within miR-17-92 is required for efficient processing of the cluster. SRSF3 depletion specifically compromises the processing of two paralog miRNAs, miR-17 and miR-20a. In addition to SRSF3 binding to the CNNC sites, the SRSF3 RS-domain is essential for miR-17-92 processing. SHAPE-MaP probing demonstrates that SRSF3 binding disrupts local and distant base pairing, resulting in global changes in miR-17-92 RNA structure. Our data suggest a model where SRSF3 binding, and potentially its RS-domain interactions, may facilitate an RNA structure that promotes miR-17-92 processing. SRSF3-mediated increase in miR-17/20a levels inhibits the cell cycle inhibitor p21, promoting self-renewal in normal and cancer cells. The SRSF3-miR-17-92-p21 pathway operates in colorectal cancer, linking SRSF3-mediated pri-miRNA processing and cancer pathogenesis.

| S-SCDT-10_15252-EMBR_202256021 | biostudies-other

OncomiRs miR-106a and miR-17 negatively regulate the nucleoside-derived drug transporter hCNT1.

Project description:High-affinity uptake of natural nucleosides as well as nucleoside derivatives used in anticancer therapies is mediated by human concentrative nucleoside transporters (hCNTs). hCNT1, the hCNT family member that specifically transports pyrimidines, is also a transceptor involved in tumor progression. In particular, oncogenesis appears to be associated with hCNT1 downregulation in some cancers, although the underlying mechanisms are largely unknown. Here, we sought to address changes in colorectal and pancreatic ductal adenocarcinoma-both of which are important digestive cancers-in the context of treatment with fluoropyrimidine derivatives. An analysis of cancer samples and matching non-tumoral adjacent tissues revealed downregulation of hCNT1 protein in both types of tumor. Further exploration of the putative regulation of hCNT1 by microRNAs (miRNAs), which are highly deregulated in these cancers, revealed a direct relationship between the oncomiRs miR-106a and miR-17 and the loss of hCNT1. Collectively, our findings provide the first demonstration that hCNT1 inhibition by these oncomiRs could contribute to chemoresistance to fluoropyrimidine-based treatments in colorectal and pancreatic cancer.

| S-EPMC8629896 | biostudies-literature

Overview of miR-106a Regulatory Roles: from Cancer to Aging.

Project description:MicroRNAs (miRNAs) comprise a class of non-coding RNA with extensive regulatory functions within cells. MiR-106a is recognized for its super-regulatory roles in vital processes. Hence, the analysis of its expression in association with diseases has attracted considerable attention for molecular diagnosis and drug development. Numerous studies have investigated miR-106 target genes and shown that this miRNA regulates the expression of some critical cell cycle and apoptosis factors, suggesting miR-106a as an ideal diagnostic and prognostic biomarker with therapeutic potential. Furthermore, the reported correlation between miR-106a expression level and cancer drug resistance has demonstrated the complexity of its functions within different tissues. In this study, we have conducted a comprehensive review on the expression levels of miR-106a in various cancers and other diseases, emphasizing its target genes. The promising findings surrounding miR-106a suggest its potential as a valuable biomolecule. However, further validation assessments and overcoming existing limitations are crucial steps before its clinical implementation can be realized.

| S-EPMC10451182 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data