Transcriptomics

Dataset Information

72

Integrated analysis of microRNA and mRNA expression and association with HIF binding in MCF-7 cells under hypoxia [mRNA]


ABSTRACT: Purpose: We aimed to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression. Methods: microRNA sequencing data and gene expression microarray data were generated from MCF-7 cells submitted to an hypoxia timecourse (16h, 32h and 48h at 1% Oxygen). Data was integrated to 500 published high-stringency HIF binding sites identified in MCF-7 cells. Results: We identified 41 microRNAs significantly up- and 28 down- regulated, of which 38 mature and 20 star forms are reported in conjunction with hypoxia for the first time. HIF-1α and HIF-2α binding sites within 50kb distance of microRNA loci were found by integration of HIF ChIP-seq data, showing overall association between binding sites and up-regulation. Gene expression profiling analysis showed no full coordination between pri-miRNA and microRNA expression, pointing towards additional levels of regulation. Several transcripts playing a role in microRNA processing were found regulated by hypoxia, of which two were HIF dependent. Conclusions: The data support the hypothesis that microRNA expression under hypoxia is regulated at transcriptional and post-transcriptional level. HIF is involved at both levels, regulating the transcription of certain microRNAs and also the expression of key elements of the microRNA processing pathway. Gene expression profiles of MCF-7 exposed to hypoxia (1% Oxygen) for 16h (3 replicates), 32h (3 replicates) and 48h (3 replicates) and to normoxia (3 replicates) were generated using Illumina microarrays.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jiannis Ragoussis   Carme Camps 

PROVIDER: E-GEOD-47533 | ArrayExpress | 2014-02-13

SECONDARY ACCESSION(S): GSE47533PRJNA205986

REPOSITORIES: GEO, ArrayExpress

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Publications

Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia.

Camps Carme C   Saini Harpreet K HK   Mole David R DR   Choudhry Hani H   Reczko Martin M   Guerra-Assunção José Afonso JA   Tian Ya-Min YM   Buffa Francesca M FM   Harris Adrian L AL   Hatzigeorgiou Artemis G AG   Enright Anton J AJ   Ragoussis Jiannis J  

Molecular cancer 20140211


In mammalians, HIF is a master regulator of hypoxia gene expression through direct binding to DNA, while its role in microRNA expression regulation, critical in the hypoxia response, is not elucidated genome wide. Our aim is to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression.MCF-7 cells were incub  ...[more]

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