Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiRNAs in ovarian cancer: A systems approach (MAS5, plier, GCRMA)

ABSTRACT: MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted mRNAs making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted messenger RNAs (mRNAs) were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ~6-11% of predicted target mRNAs. Our results underscore the complexities of miRNA-mediated regulation in vivo and caution against the widespread clinical application of miRNAs and miRNA inhibitors until the basis of these complexities is more fully understood. mRNAs were collected from 3 miR-7 treated, 2 miR-128 treated , and 3 negative control miRNA treated HEY ovarian cancer cell samples. The mRNA expression pattern was compared between the miR-7 treated cells and the negative control treated cells, and separately between the miR-128 treated cells and the negative control treated cells using the Affymetrix U133 Plus 2.0 3' expression array.

ORGANISM(S): Homo sapiens

SUBMITTER: Shubin Shahab

PROVIDER: E-GEOD-27431 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

MicroRNAs may indirectly regulate other microRNAs

Project description:MicroRNAs (miRNAs) are a class of regulatory RNAs that control the expression of genes critical to cell function. Ectopic expression of miRNAs has been shown to result in genome-wide changes in patterns of gene expression. While the reasons for these global alterations in gene expression patterns have been attributed to the ability of miRNAs to target multiple genes, and/or to induce indirect effects downstream of target genes, the molecular basis of indirect effects of miRNA regulation remains poorly understood. In this study, we demonstrate the potential of miRNAs to regulate other miRNAs. Using miRNA microarray analysis, we show that over 70 different miRNAs are differentially expressed ( M-bM-^IM-%1.4 fold, FDR M-bM-^IM-$ 5%) in human ovarian cancer cells after transfection with a single miRNA (miR-7). We present evidence that a major component of miR-7-induced changes in levels of miRNAs is the indirect consequence of miR-7-mediated alterations in levels of protein-coding genes (e.g., transcription and splicing factors) that exert trans-regulatory control on miRNAs. HEY cells were transfected with either hsa-miR-7 (2 biological replicates) or a negative control miRNA, miR-NC (2 biological replicates), and then grown in 6-well plates for ~48 hours. The difference in miRNA expression pattern between the miR-7-transfected cells and the miR-NC-transfected cells was determined using an Affymetrix GeneChip miRNA Array.

2012-04-08 | E-GEOD-29129 | biostudies-arrayexpress

Impact of miRNAs on the USSC proteome after XXL-differentiation

Project description:The contribution of microRNA-mediated posttranscriptional regulation on the final proteome in differentiating cells remains elusive. Here, we evaluated the impact of microRNAs (miRNAs) on the proteome of human umbilical cord blood-derived unrestricted somatic stem cells (USSC) during retinoic acid (RA) differentiation by a systemic approach using next generation sequencing analysing mRNA and miRNA expression and quantitative mass spectrometry-based proteome analyses. Interestingly, regulation of mRNAs and their dedicated proteins highly correlated during RA-incubation. Additionally, RA-induced USSC demonstrated a clear separation from native USSC thereby shifting from a proliferating to a metabolic phenotype. Bioinformatic integration of up- and downregulated miRNAs and proteins initially implied a strong impact of the miRNome on the XXL-USSC proteome. However, quantitative proteome analysis of the miRNA contribution on the final proteome after ectopic overexpression of downregulated miR-27a-5p and miR-221-5p or inhibition of upregulated miR-34a-5p, respectively, followed by RA-induction revealed only minor proportions of differentially abundant proteins. In addition, only small overlaps of these regulated proteins with inversely abundant proteins in non-transfected RA-treated USSC were observed. Hence, mRNA transcription rather than miRNA-mediated regulation is the driving force for protein regulation upon RA-incubation, strongly suggesting that miRNAs are fine-tuning regulators rather than active primary switches during RA-induction of USSC.

2020-01-31 | PXD016915 | Pride

Reintroduction of miRNAs into Dgcr8 deficient cell lines to generate miRNA target lists

Project description:These experiments were conducted as part of a study to derive the targets of miRNAs (See also E-MTAB-418). Two independent BayGenomics mouse embryonic stem cell lines (XH157 and XG058), each bearing a gene trap between exons 9 and 10 of the Dgcr8 locus (ENSMUST00000115633, Ensembl v53) were further mutagenised by the targetted insertion of a second Dgcr8 gene trap cassette. Consequently two independent heterozygous and two independent homozygous mutant Dgcr8 cells were derived (Dgcr8tm1,gt1/+, Dgcr8tm1,gt2/+, Dgcr8gt1/tm1 and Dgcr8gt2/tm1). Subsequently individual miRNA mimics were reintroduced into the Dgcr8-depleted background. In this set of experiments, cells were allowed to recover for 10 hours. The effect of the miRNA on the mRNA expression of the cells was assessed through the comparison of the expression profile of the transfected cells to that of cells transfected with a control mimic, which had recovered over the same period. This allows the roles of individual miRNAs to be investigated.

2012-08-20 | E-MTAB-968 | biostudies-arrayexpress

Comparison of gene expression between MIA PaCa-2 cells transfected with miR-4653-3p mimic and negative control cells

Project description:To identify the target of miR-4653-3p, mRNA microarray analysis was performed to compare mRNA expression between MIA PaCa-2 cells transfected with miR-4653-3p mimic and negative control cells.

2023-05-28 | E-MTAB-11813 | biostudies-arrayexpress

Transcription profiling by array of mouse embryonic stem cell lines with Dgcr8 mutations to investigate the broad role of miRNAs and individual miRNAs through the reintroduction of miRNA mimics

Project description:These experiments were conducted as part of a study to derive the targets of miRNAs. Two independent BayGenomics mouse embryonic stem cell lines (XH157 and XG058), each bearing a gene trap between exons 9 and 10 of the Dgcr8 locus (ENSMUST00000115633, Ensembl v53) were further mutagenised by the targetted insertion of a second Dgcr8 gene trap cassette. Consequently two independent heterozygous and two independent homozygous mutant Dgcr8 cells were derived (Dgcr8tm1,gt1/+, Dgcr8tm1,gt2/+, Dgcr8gt1/tm1 and Dgcr8gt2/tm1). A comparison of the expression profiles of the heterozygous cells to the Dgcr8 depleted cells allows the investigation of the broad role of miRNAs in mouse ES cells. Subsequently individual miRNA mimics were reintroduced into the Dgcr8-depleted background. The cells were allowed to recover for 10, 20 or 44 hours. The effect of the miRNA on the mRNA expression of the cells was assessed through the comparison of the expression profile of the transfected cells to that of cells transfected with a control mimic, which had recovered over the same period. This allows the roles of individual miRNAs to be investigated.

2012-08-20 | E-MTAB-418 | biostudies-arrayexpress

Functional and evolutionary significance of human microRNA seed region mutations [miR-429]

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the regulation of gene expression at the post transcriptional and/or translational level thus impacting various biological processes. Dysregulation of miRNAs could affect processes associated with progression of a variety of diseases including cancer. Majority of miRNA targeting in animals involves a 7-nt M-bM-^@M-^\seed regionM-bM-^@M-^] mapping to positions 2-8 at the moleculeM-bM-^@M-^Ys 5' end. The importance of this 7 nt sequence to miRNA function is evidenced by the fact that the seed region sequence of many miRNAs is highly conserved within and between species. In this study, we computationally and experimentally explore the functional significance of sequence variation within the seed region of human miRNAs. Our results indicate that change of a single nt within the 7-nt seed region changes the spectrum of targeted mRNAs significantly meanwhile further nt changes have little to no additional effect. This high functional cost of even a single nucleotide change within the seed region of miRNAs explains why the seed sequence is highly conserved among many miRNA families both within and between species and could help clarify the likely mechanisms underlying the evolution of miRNA regulatory control. mRNAs were collected from 3 miR-429 treated and 3 negative control miRNA treated HEY ovarian cancer cell samples. mRNA expression was captured on Affymetrix U133 Plus 2 chips. To compare mRNA expression pattern between the miR-429 treated cells and the negative control treated cells, present/absent calls were generated using MAS5, while signals were calculated using GCRMA and then log2 transformed. Expression of differentially expressed genes or down regulated miRanda-mirSVR predicted miRNA target genes was compared between miRNA treated samples.

2015-01-30 | E-GEOD-56967 | biostudies-arrayexpress

Project description:Age-related changes in microRNA levels in serum 20 nM biotinylated miRIDIAN miR-1248 mimic (Thermo Scientific) or a negative control, biotinylated miRIDIAN C. elegans miR-67 (here named Con-miR) using Lipofectamine 2000. Forty eight hours post transfection, total RNA was isolated using the mirVana kit (Invitrogen) according to manufacturer’s procedure. Three replicate experiments were performed and a technical repeat was included for each sample. Samples were analyzed using Illumina's Sentrix Human HT-12 ver4 Expression BeadChips (Illumina, San Diego, CA).

2013-10-09 | E-GEOD-51309 | biostudies-arrayexpress

Human Papillary thyroid cancer cell line, BCPAP control vs. miR-146b-5p mimic transfected

Project description:Transcriptional profiling of human papillary thyroid cancer cells comparing control untreated BCPAP cells with BCPAP cells transfected with miR-145b-5p mimic. Two-condition experiment, BCPAP cells vs. miR-146b-5p transfexted BCPAP cells. Biological replicates: 1 control sample, 1 transfected sample.

2015-12-17 | E-GEOD-76050 | biostudies-arrayexpress

p53-regulated networks of protein, mRNA, miRNA and lncRNA expression revealed by integrated pSILAC and NGS analyses

Project description:We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics of newly synthesized proteins (pulsed stable isotope labeling with amino acids in cell culture, pSILAC) in combination with mRNA and non-coding RNA expression analyses by next generation sequencing (RNA-, miR-Seq) in the colorectal cancer (CRC) cell line SW480. Furthermore, genome-wide DNA binding of p53 was analyzed by chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated mRNAs (1258 up, 415 down), miRNAs (111 up, 95 down), lncRNAs (270 up, 123 down) and proteins (542 up, 569 down). Changes in mRNA and protein expression levels showed a positive correlation (r = 0.50, p < 0.0001). More transcriptionally induced genes displayed occupied p53 binding sites (4.3% mRNAs, 7.2% miRNAs, 6.3% lncRNAs, 5.9% proteins) than repressed genes (2.4% mRNAs, 3.2% miRNAs, 0.8% lncRNAs, 1.9% proteins), suggesting indirect mechanisms of repression. Around 50% of the downregulated proteins displayed seed-matching sequences of p53-induced miRNAs in the corresponding 3â??-UTRs. Moreover, proteins repressed by p53 significantly overlapped with those previously shown to be repressed by miR-34a. We confirmed upregulation of the novel direct p53 target genes LINC01021, MDFI, ST14 and miR-486 and showed that ectopic LINC01021 expression inhibited proliferation in SW480 cells. Furthermore, HMGB1, KLF12 and CIT mRNAs were confirmed as direct targets of the p53-induced miR-34a, miR-205 and miR-486-5p, respectively. In line with the loss of p53 function during tumor progression, elevated expression of HMGB1, KLF12 and CIT was detected in advanced stages of cancer. This study provides new insights and a comprehensive catalogue of p53-mediated regulations and p53 DNA binding in CRC cells.

2016-05-24 | MSV000079767 | MassIVE

Identification of miR-16/29 targets in adipocytes by LC-MSMS

Project description:Cancer cachexia is a multifactorial metabolic syndrome defined by the rapid loss of skeletal muscle mass and the loss of fat mass. Up 80% of cancer patients at the late stage with cachexia suffer from progressive atrophy of adipose tissue. Unlike studies on skeletal muscle wasting, there is limited research on fat loss in cachexia. It was noted that most patients suffer from fat loss as cancer progress. Fat loss precedes muscle loss, is associated with shorter survival, and is variable to timing and intensity in various cancer populations. Increased lipolysis may be the leading cause of fat loss in cancer cachexia. miRNAs are a class of non-coding RNAs of 19~25 nucleotides that regulate gene silencing by interacting with the 3’ untranslated region (UTR) of target mRNA to cause mRNA degradation and translational repression. miRNAs play multifaceted roles in pancreatic cancer proliferation, survival, metastasis, and chemoresistance. Aberrant expression of miRNA in circulating exosomes may play potential roles in modulating fat loss in cancer cachexia. We identified 2 miRNAs, miR-16 and miR-29, which have 2-fold higher expression existed in at PDAC cells. To explore which genes in adipogenesis and lipolysis were directly affected by miR-16-5p or/and miR-29a-3p, we analyzed the targets which were down-regulated in both miR-16-5p and miR-29a-3p-transfected 3T3-L1 cells by mass analysis.

2024-06-13 | PXD037998 | Pride

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