Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Hepatic gene expression changes following antisense oligonucleotide-based inhibition of miR-29a

ABSTRACT: Adult BALB/c female mice were injected intraperitoneally with a single dose at 20 mg per kg of antisense oligonucleotide either against miR-29a (5’-TAACCGATTTCAGATGGTGCTA-3’) or against a scrambled sequence (5’-TCATTGGCATGTACCATGCAGCT-3’ Antisense oligonucleotides contained 2’-O-methoxyethyl (2’-MOE), 2’-flouro (2’-F) 2'-alpha-flouro units with a phosphorothioate backbone (Regulus Therapeutics). Six days following the injection, liver was isolated, total RNA was prepared as described above, and the RNA was amplified and biotinylated using the MessageAmp Premier kit (Ambion). Samples (n=4 each experimental and control) were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Arrays in the Children’s Hospital of Philadelphia Nucleic Acids Core Facility and analyzed with the assistance of the Penn Bioinformatics Core. Probe intensities were normalized using the GCRMA method and the significance of the log2-transformed, GCRMA-normalized signal intensities was determined using SAM Adult mice injected with anti-miR-29a or scrambled control ASO, n=4 per group

ORGANISM(S): Mus musculus

SUBMITTER: Joshua Friedman

PROVIDER: E-GEOD-40261 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia.

Hand Nicholas J NJ Horner Amber M AM Master Zankhana R ZR Boateng LaTasha A LA LeGuen Claire C Uvaydova Marina M Friedman Joshua R JR

Journal of pediatric gastroenterology and nutrition 20120201 2

Biliary atresia (BA) is a pediatric liver disease of unknown underlying etiology, in which fibroinflammatory destruction of the extrahepatic biliary system leads to obstructive cholestasis. MicroRNAs are a class of short (18-23 nucleotide), noncoding RNA molecules, which act as negative regulators of target mRNA stability and translation. The importance of these molecules in normal and diseased liver has been demonstrated, but their potential role in the pathogenesis of BA has not been addressed ...[more]

PMID: 22167021

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Project description:The miR-29 family is an important player in the molecular pathophysiology of distinct types of cancer, with roles that seems to depend on cellular context. Reduced miR-29 levels are associated with more aggressive disease and its overexpression in cancer and leukemic cell lines inhibits proliferation. In contrast, its overexpression in hematopoietic progenitors, promotes leukemogenesis. We explored the potential roles of miR-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL). As compared to normal T-cells, miR-29a levels are extremely reduced in T-ALL and in the Jurkat cell line. Microarrays analysis in Jurkat cells, following the introduction of synthetic miR-29a mimics, revealed the down-regulation of several predicted targets, including previously described targets (DNMT3a/b, CDK6, PXDN, MCL1, PIK3R1 and CXXC6), and novel targets with roles in active DNA demethylation, such as members of the ten-eleven-translocation (TET) family and TDG. Reduced miR-29a levels contribute to altered epigenetics, as its introduction in Jurkat cells, promotes the demethylation of the AHR gene (commonly methylated in T-ALL). In T-ALL patients, miR-29a levels are significantly associated with blast counts and disease free survival. Our results highlight the relevance of miR-29 in T-ALL physiopathology, and may help to clarify some contrasting findings reported in the literature. In order to identify potential miR-29a targets in T-cell lymphoblastic leukemia, Jurkat cells were electroporated with synthetic RNA molecules corresponding to miR-29a mimics (pre-miR) or inhibitors (anti-miR); and microarray profiles were compared to the profiles of Jurkat cells eletroporated with the corresponding negative controls. Transcripts with levels reduced following the introduction of the pre-miR-29a (as compared to pre-miR-Control), or transcripts acumulated folowing introduction of the anti-miR-29a inhibitor (as compared to anti-miR-Control), were considered potential targets; and were further compared to microRNA target prediction databases. Two paired samples were used for this analysis.

Dataset Information

Hepatic gene expression changes following antisense oligonucleotide-based inhibition of miR-29a

Publications

MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia.

Similar Datasets

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