Transcriptomics,Multiomics

Dataset Information

6

Small RNA-seq and gene expression analysis reveal a miRNA profile of cancer-susceptibility in ATM deficient human mammary epithelial cells (Small RNA-Seq)


ABSTRACT: Deficiencies in the ATM gene are the underlying cause for ataxia telangiectasia, a congenital syndrome characterized by neurological, motor and immunological defects, as well as a predisposition to cancer risks. MicroRNAs (miRNAs) are small regulators of post-transcriptional gene expression and a useful tool for cancer diagnosis, staging, and prediction of therapeutic responses to clinical regimens. In particular, miRNAs have been used to develop signatures for breast cancer profiling. We are interested in the consequences of ATM deficiency on miRNA expression in breast epithelial cells and the potential contribution to cancer predisposition. In this study we investigate the effects of ATM loss on the miRNA expression and related gene expression changes in normal human mammary epithelial cells (HME-CC). We have identified 81 significantly differently expressed miRNAs in the ATM-deficient HME-CCs using small RNA sequencing. Many of these differentially expressed miRNAs have been described and implicated in tumorigenesis and proliferation. These changes include down-regulation of tumor suppressor miRNAs, such as hsa-miR-29c and hsa-miR-16, as well as the over-expression of pro-oncogenic miRNAs hsa-miR-93 and hsa-mir-221. All 81 miRNAs were combined with genome wide gene expression profiles to investigate possible targets of miRNA regulation. We identified messenger RNA (mRNA) targets of these miRNAs that were also significantly regulated after the depletion of ATM. Predicted targets included many genes implicated in cancer formation and progression, including SOCS1 and the proto-oncogene MAF. Integrated analysis of miRNA and mRNA expression allows us to build a more complete understanding of the pathways and networks involved in the breast cancer predisposition observed in individuals deficient in ATM. This study highlights miRNA and predicted mRNA target expression changes in ATM-deficient HME-CCs and suggests a mechanism for the breast cancer-prone phenotype seen in ATM deficient cells and patients. Additionally, this study provides preliminary data for defining miRNA profiles that may be used prognostic biomarkers for breast cancer predisposition. Examination of small RNA population in human mammary epithelial cell lines. Each condition was preformed in triplicate.

OTHER RELATED OMICS DATASETS IN: PRJNA155815PRJNA155733E-GEOD-36082PRJNA153095

ORGANISM(S): Homo sapiens  

SUBMITTER: Cynthia L Innes   Liwen Liu  NIEHS Microarray Core  Jill E Hesse  Richard S Paules 

PROVIDER: E-GEOD-36266 | ArrayExpress | 2013-08-22

SECONDARY ACCESSION(S): SRP011278GSE36266PRJNA155815

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Genome-wide small RNA sequencing and gene expression analysis reveals a microRNA profile of cancer susceptibility in ATM-deficient human mammary epithelial cells.

Hesse Jill E JE   Liu Liwen L   Innes Cynthia L CL   Cui Yuxia Y   Palii Stela S SS   Paules Richard S RS  

PloS one 20130531 5


Deficiencies in the ATM gene are the underlying cause for ataxia telangiectasia, a syndrome characterized by neurological, motor and immunological defects, and a predisposition to cancer. MicroRNAs (miRNAs) are useful tools for cancer profiling and prediction of therapeutic responses to clinical regimens. We investigated the consequences of ATM deficiency on miRNA expression and associated gene expression in normal human mammary epithelial cells (HME-CCs). We identified 81 significantly differen  ...[more]

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