MicroRNA-27a contributes to rhabdomyosarcoma cell proliferation through suppression of RARA and RXRA
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE52679
PROVIDER: PRJNA229773 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Background: Rhabdomyosarcomas (RMS) are rare but very aggressive tumors of childhood that arise as a consequence of regulatory distruption of the growth and differentiation pathways of myogenic precursor cells. Based on morphology, two major RMS subtypes can be identified: embryonal RMS (ERMS) and alveolar (ARMS). So, it is essential to unravel the molecular mechanisms involved in cancer pathogenesis and in disease progression. MicroRNAs are endogenous small non-coding RNAs with a key role in tumorigenesis. Methodology/Principal Findings: To better understand the involvement of miRNAs in RMS, we analyzed the expression profile of 8 different RMS cell lines (4 ARMS and 4 ERMS). The miRNA population from each cell line was compared to a reference sample consisting of a pool of each total RNA sample mixed in equal amount. We identified a 16 miRNAs signature that discriminates translocation positive (ARMS) and negative RMS (ERMS). We focused our attention on the role of miR-27a that is up-regulated in the more aggressive RMS cell lines (ARMS translocation positive) where probably it acts as an oncogene. miR-27a-overexpressing cells showed a significant enhance of the proliferation rate, paralleled by a decrease of cells in G1 phase. We demonstrated that miR-27a is implicated in cell cycle control by targeting the retinoic acid alpha receptor (RARA) and retinoic X receptor alpha (RXRA). Conclusions: Our results demonstrated the potential of miRNA expression signature to better classify different RMS subtypes and settled the basis for a potential therapeutic role of miR-27a in RMS through modulation of retinoic acid receptors expression.
2015-05-04 | GSE52679 | GEO
Project description: Not available
| S-EPMC4410939 | biostudies-literature
Project description:The experimental design was to determine the regulon of the transcriptional activator RarA. This was done by comparing the transcriptome profiles between a rarA overexpressor and the baseline control. RarA overexpression was achieved by plasmid mediated overexpression of the rarA gene and the baseline control was a vector only strain.
2013-03-21 | E-MEXP-3742 | biostudies-arrayexpress
Project description:For the genome-wide analysis using ChIP-Seq on mouse liver cells, a full accounting of all RXRα binding sites and of RXRa related gene regulations is expected to address the main knowledge gap around RXRα. Liver tissue of wild type and hs-RXRa-del-exon4-/- mice, male and female for each genotype have been ChIP-Seq'ed for RXRa and Pol2.
2014-04-01 | E-GEOD-21696 | biostudies-arrayexpress
Project description:Astrammina rara Genome sequencing and assembly
| PRJNA521081 | ENA
Project description:RARA haploinsufficiency is an invariable consequence of t(15;17) reciprocal translocations in acute promyelocytic leukemia (APL). Furthermore, retinoids and RARA activity have been implicated in hematopoietic self-renewal, lineage commitment and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis we crossed RARA+/- mice with mice expressing PML-RARA from the Cathepsin G locus (mCG-PR). We found that RARA haploinsufficiency cooperated with PML-RARA, only modestly influencing the pre-leukemic and leukemic phenotype. Bone marrow from mCG-PR+/- x RARA+/- mice had decreased numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation and an increased competitive advantage following transplantation. RARA haploinsufficiency did not alter mCG-PR dependent leukemic latency or penetrance, but did influence the distribution of leukemic cells; mCG-PR+/- x RARA+/- mice presented more commonly with low to normal white blood cell counts and with myeloid infiltration of lymph nodes. APL arising in these mice was responsive to ATRA, and had virtually no differences in expression profiling compared to tumors arising in mCG-PR+/- x RARA+/+ mice. These phenotypes were dependent on PML-RARA activity, since they were not detected in RARA+/- mice in the absence of the mCG-PR transgene. These data show that RARA haploinsufficiency (like PML haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis and phenotype of APL in mice, but that PML-RARA is the driver of t(15;17) APL.
2010-07-29 | GSE23291 | GEO
Project description:Transcriptional profiling of murine cells expressing PML/RARA at the early promyelocyte stage (4 weeks old, preleukemic) and in full blown PML/RARA leukemia generated by transducing PML/RARA bone marrow with a Flt3-ITD retroviral vector
2015-07-15 | GSE59431 | GEO
Project description:RARA haploinsufficiency is an invariable consequence of t(15;17) reciprocal translocations in acute promyelocytic leukemia (APL). Furthermore, retinoids and RARA activity have been implicated in hematopoietic self-renewal, lineage commitment and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis we crossed RARA+/- mice with mice expressing PML-RARA from the Cathepsin G locus (mCG-PR). We found that RARA haploinsufficiency cooperated with PML-RARA, only modestly influencing the pre-leukemic and leukemic phenotype. Bone marrow from mCG-PR+/- x RARA+/- mice had decreased numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation and an increased competitive advantage following transplantation. RARA haploinsufficiency did not alter mCG-PR dependent leukemic latency or penetrance, but did influence the distribution of leukemic cells; mCG-PR+/- x RARA+/- mice presented more commonly with low to normal white blood cell counts and with myeloid infiltration of lymph nodes. APL arising in these mice was responsive to ATRA, and had virtually no differences in expression profiling compared to tumors arising in mCG-PR+/- x RARA+/+ mice. These phenotypes were dependent on PML-RARA activity, since they were not detected in RARA+/- mice in the absence of the mCG-PR transgene. These data show that RARA haploinsufficiency (like PML haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis and phenotype of APL in mice, but that PML-RARA is the driver of t(15;17) APL. RARA+/- mice were crossed with mice expressing PML-RARA from Cathepsin G locus (mCG-PR). Five leukemic mice were chosen from each of the mCG-PR+/-RARA+/- and mCG-PR+/-RARA+/+ strains and total RNA extracted from the spleen samples were analyzed using Affymetrics Mouse Exon 1.0 platform
2010-07-29 | E-GEOD-23291 | biostudies-arrayexpress
Project description:Acute promyelocytic leukemia (APL) is associated with PML-RARA expression and late myeloid maturation arrest. The myeloid restriction of PML-RARA dependent leukemia has been recapitulated in multiple mouse models of APL, including PML-RARA expressed from the Ctsg locus (mCG-PR). However, we report here that Ctsg expression is not limited to promyelocytes (as had previously been thought); Ctsg RNA is detectable in KLS cells, and mCG-PR mice express PML-RARA within the same compartment, an event that alters multilineage hematopoiesis. However, these animals only develop myeloid leukemia (consistent with the myeloid restriction of human PML-RARA-associated leukemia). Our results suggest that APL is shaped by myeloid- and development-specific factors that define the ultimate leukemic phenotype rather than PML-RARA acting in a committed myeloid precursor.
2010-10-21 | GSE24728 | GEO