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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MiR-99a let7c cluster

ABSTRACT: To investigate the function of miR99a/let-7c miRNAs during cardiomyogenesis, we decided to perturb their expression using transgenic mES cell lines the corresponding precursors (pre-miRNA) of the two miRNAs. We used the ROSA-TET system (EB3 tet off), in which the transgene is inserted in Rosa26 locus by Cre recombinase. We generated three different clones both miRNAs let-7c/miR-99a and those only one miRNA, namely the let-7cdeletedmiR-99a and the miR-99adeletedlet-7c.

ORGANISM(S): Mus musculus

SUBMITTER: Gilda Cobellis

PROVIDER: E-MEXP-3748 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications.

Coppola Antonietta A Romito Antonio A Borel Christelle C Gehrig Corinne C Gagnebin Maryline M Falconnet Emilie E Izzo Antonella A Altucci Lucia L Banfi Sandro S Antonarakis Stylianos E SE Minchiotti Gabriella G Cobellis Gilda G

Stem cell research 20131128 2

Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem ce ...[more]

PMID: 24365598

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miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFM-NM-2 and Wnt signaling

Project description:Although regulation of stem cell homeostasis by miRNAs is well studied, it is unclear how individual miRNAs, genomically encoded within an organized polycistron, can interact to induce an integrated phenotype. miR-99a/100, let-7 and miR-125b paralogues are encoded in two tricistrons on human chromosome 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Integrative analysis of global gene expression profiling, miRNA target prediction and pathway architecture revealed that miR-99a/100, let-7 and miR-125b functionally converge at the combinatorial block of the TGFM-NM-2 pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, downregulation of tumor suppressor genes APC/APC2 stabilizes active M-NM-2-Catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFM-NM-2 signaling the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo, while favoring megakaryocytic differentiation. We lentivirally transduced cord blood CD34+-hematopoietic stem and progenitor cells (CB-HSPCs) to ectopically express miR-125b-2, miR-99a, let-7c or miR-99a~125b-2 and cultured them in megakaryocytic differentiation medium for 7 days.

2014-03-28 | E-GEOD-56335 | biostudies-arrayexpress

Down modulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma

Project description:Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date few molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed on 26 unresected MPM with distinct clinical outcome: 15 patients had aggressive disease (OS<12 months) and 11 patients indolent disease (OS>36 months). Three prognostic miRNAs (mir-99a, let-7c and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data (TCGA) from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high risk score was an independently associated with shorter OS (HR=3.14; 95% CI, 1.18–8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

2017-07-28 | GSE92636 | GEO

Expression data from inducible ES stable cell line

Project description:In order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the inducible not-tagged cell line. Transcriptome analysis of the inducible transgenic mouse ES cell line. The E13 inducible cell lines derived from parental EB3 cell line. The cell line EB3 was obtained from the laboratory of Dr Hitoshi Niwa as previously described in (Masui S et al., 2005). Tthe specific mouse gene is E130012A19Rik. For the analysis on the inducible not-tagged cell line, total RNA was extracted from three biological replicates grown in medium deprived of Tetracycline for 48 hours; RNA extracted from un-induced clones was used as control.

2012-12-13 | E-GEOD-31166 | biostudies-arrayexpress

Expression data after miR-99a transfection in C4-2 prostate cancer cells

Project description:MicroRNAs (miRNAs) have been globally profiled in cancers but there tends to be poor agreement between studies including in the same cancers. Additionally, few putative miRNA targets have been validated. To overcome the lack of reproducibility, we profiled miRNAs by next generation sequencing and locked nucleic acid miRNA microarrays, and we verified concordant changes by quantitative RT-PCR. Notably, miR-125b and the miR-99 family members miR-99a, -99b, -100 were down-regulated in all assays in advanced prostate cancer cell lines relative to the parental cell lines from which they were derived. All four miRNAs were also down-regulated in human prostate tumor tissue compared to normal prostate. Transfection of miR-99a, -99b or -100 inhibited the growth of prostate cancer cells and decreased the expression of prostate-specific antigen (PSA), suggesting potential roles as tumor suppressors in this setting. To identify targets of these miRNAs, we combined computational prediction of potential targets with experimental validation by microarray and polyribosomal loading analysis. Three direct targets of the miR-99 family that were validated in this manner were the chromatin remodeling factors SMARCA5 and SMARCD1 and the growth regulatory kinase mTOR. We determined that PSA is post-transcriptionally regulated by the miR-99 family members at least partially by repression of SMARCA5. Together, our findings suggest key functions and targets of miR-99 family members in prostate cancer suppression and prognosis. C4-2 cells were transfected with miR-99a and harvested after 48hr. si-GL2 was used as control.

2010-12-29 | E-GEOD-26332 | biostudies-arrayexpress

Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3 (RNA-Seq data)

Project description:We report that TAF3, a TBP-associated core promoter factor, is highly enriched in ES cells. In addition to its role in the core promoter recognition complex TFIID, genome-wide binding studies reveal that TAF3 localizes to chromosomal regions bound by CTCF and cohesin. Enrichment for TAF3/CTCF/cohesin bound regions distinguishes TAF3-activated from TAF3-repressed genes. Our findings support a new role of TAF3 in mediating long-range chromatin regulatory interactions to safeguard the finely-balanced transcriptional programs that give rise to pluripotency. Comparison of genome-wide expression patterns between TAF3-knockdown and WT embryonic stem cells using mRNA-Seq. Significantly differentially expressed protein-coding genes were identified by comparing control and knock-down samples at each timepoint (ES, embryoid body day 3 (EB3), EB6). Single and paired-end samples were combined at each timepoint, resulting in 3 tests for each gene (based on 8, 4, 4 independent measurements at ES ,EB3, EB6, respectively).

2011-09-02 | E-GEOD-31271 | biostudies-arrayexpress

Vibrio diazotrophicus strain:99A

Project description:Vibrio diazotrophicus 99A genome sequencing

| PRJNA456207 | ENA

Expression data from inducible ES stable cell lines

Project description:In order to identify the effects of the induction of the gene of interest on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the different inducible cell lines Transcriptome analysis of the inducible transgenic mouse ES cell lines For the analysis on the different inducible cell lines, total RNA was extracted from three biological replicates grown in medium deprived of Tetracycline for 17 and 24 hours; RNA extracted from un-induced clones was used as control. Total RNA extracted from parental cell line EBRTcH3 (EB3) was used as additional control.

2012-12-03 | E-GEOD-32015 | biostudies-arrayexpress

Expression data from ETV6-RUNX1-positive Reh leukemic cells after overexpression of miR-125b, miR-100 and miR-99a levels in different combinations

Project description:Combined overexpression of miR-125b with miR-99a and/or miR-100 induced VCR resistance in ETV6-RUNX1-positive leukemic cells Reh. We used microarrays to detail the global changes in gene expression of Reh cells upon enforced expression of miR-125 per se compared with combination of overexpression of miR-125b, miR-100 and/or miR-99a MiR-99a and/or miR-100 were transiently overexpressed in stable miR-125b-expressing and stable scrambled miR-control-expressing Reh cells. Cellular resistance to VCR was determined by MTT assay after incubating the cells with 9 ng/mL VCR for 3 days. Changes in the gene expression pattern of Reh cells induced by miRNAs overexpression were measured using Affymetrix Arrays.

2013-06-27 | E-GEOD-46362 | biostudies-arrayexpress

Expression data after miR-99a transfection in C4-2 prostate cancer cells

2010-12-29 | GSE26332 | GEO

miRNA expression in human tracheal smooth muscle

Project description:We surveyed miRNA expression in intact airway smooth muscle tissue to evaluate candidate miRNA for further studies. We found 60 miRNA expressed at a detectable level in all four donors and another 118 miRNA expressed in three of the four donors. There were 18 miRNAs with expression levels > 2-fold above normalized expression values. These consisted of 12 described human miRNA, including let-7c, miR-16, -23b, -24, -26a, -125b, -143, -145, -200c and -205; 3 mouse miRNAs including miR-99a, -140* and -370; and 3 novel miRNA termed abi-13143, -13232 and -13268.

2009-07-22 | GSE16586 | GEO

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