Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiRNA expressions in non-cancerous and cancerous human gastric tissues

ABSTRACT: We investigated the involvement of microRNAs (miRNAs) in gastric cancers. MiRNA expression was profiled from 40 cancerous and 40 non-cancerous tissues obtained from the National Cancer Centre, Singapore, and Singhealth Tissue Repository, Singapore. We identified 80 differentially expressed miRNAs in tumors compared with normal tissues. Among these miRNAs, we identified hsa-mir-486-5p (mir-486) as a significantly downregulated miRNA in GC. Subsequent functional characterization revealed that mir-486 playing a tumor suppressor role. We also observed frequent genomic deletion of mir-486 in 20-30% of GCs. To our knowledge, mir-486 represents one of the first tumor suppressor miRNAs in GC inactivated through genomic deletion. MiRNA expression was profiled on Agilent Human miRNA Microarrays (V2) representing 723 human and 76 human viral miRNAs in 40 normal and 40 cancerous gastric tissues.

ORGANISM(S): Homo sapiens

SUBMITTER: Chia-Huey Ooi

PROVIDER: E-GEOD-23739 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.

Oh Hue-Kian HK Tan Angie Lay-Keng AL Das Kakoli K Ooi Chia-Huey CH Deng Nian-Tao NT Tan Iain Beehuat IB Beillard Emmanuel E Lee Julian J Ramnarayanan Kalpana K Rha Sun-Young SY Palanisamy Nallasivam N Voorhoeve P Mathijs PM Tan Patrick P

Clinical cancer research : an official journal of the American Association for Cancer Research 20110317 9

<h4>Purpose</h4>MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC).<h4>Experimental design</h4>Using Agilent miRNA microarrays, we compared miRNA expression profiles of 40 primary gastric tumors and 40 gastric normal tissues, identifying miRNAs significantly downregulated in gastric tumors.<h4>Results</h4>Among the top 80 miRNAs differentially expressed between gastric tumors and ...[more]

PMID: 21415212

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Project description:The transcription factor c-Myb plays a key role in human primary CD34+ hematopoietic progenitor cells (HPCs) lineage choice, by enhancing erythropoiesis at the expense of megakaryopoiesis. We previously demonstrated that c-Myb affects erythroid versus megakaryocyte lineage decision in part by transactivating KLF1 and LMO2 expression. To further unravel the molecular mechanisms through which c-myb affects lineage fate decision, we profiled the miRNA and mRNA changes in myb-silenced CD34+ HPCs. The integrative analysis of miRNA/mRNA expression changes upon c-myb silencing in human CD34+ HPCs highlighted a set of 19 miRNA with 150 anticorrelated putative target mRNAs. Among the miRNAs downregulated in myb-silenced progenitors with the highest number of predicted target mRNAs, we selected hsa-miR-486-3p based on the in vitro effects of its overexpression on HPCs commitment. Indeed, morphological and flow cytometric analyses after liquid culture showed that hsa-miR-486-3p overexpression in HPCs enhanced erythroid and granulocyte differentiation while restraining megakaryocyte and macrophage differentiation. Moreover, collagen-based clonogenic assay demonstrated a strong impairement megakaryocyte commitment upon hsa-miR-486-3p overexpression in CD34+ cells. Moreover, in order to identify the mRNA target through which hsa-miR-486-3p affects lineage fate decision, we profiled the mRNA changes in mimic transfected CD34+ HPC by means of Affymetrix GeneAtlas U219 strip array. Gene expression profiling of hsa-miR-486-3p overexpressing CD34+ cells enabled us to identify a set of 8 genes downregulated and computationally predicted, putative hsa-miR-486-3p targets. Among them, we selected c-maf transcript as upregulated upon myb silencing. Worth of note, c-maf silencing in CD34+ progenitor cells was able to reverse the affects of myb silencing on erythroid versus megakaryocyte lineage choice. Integrative miRNA/mRNA analysis highlighted a set of miRNAs and anticorrelated putative target mRNAs modulated upon myb silencing, therefore potential players in myb-driven HPCs lineage choice. Among them, we demonstrated the hsa-miR-486-3p/c-maf pair as partially contributing to the effects of myb on HPCs commitment. Therefore, our data collectively identified myb-driven hsa-miR-486-3p upregulation and subsequent c-maf downregulation as a new molecular mechanism through which cMyb favours erythropoiesis while restraining megakaryopoiesis. Gene expression profile (GEP) was performed on total RNA derived from three independent experiments at 24h after the last nucleofection.

Dataset Information

MiRNA expressions in non-cancerous and cancerous human gastric tissues

Publications

Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.

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