RUNX2 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
PCSK9 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
AKIRIN1 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
IRAK3 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
AGO4 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
MFI2 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
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. This submission represents the transcriptome component of study.
SLIT2 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
SNX22 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
RHOV UP in 'expressing ATM shRNA' vs 'expressing LacZ'
CD109 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
TFPI DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
ADAP2 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
MPHOSPH8 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
CLEC2B DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
(Factor value) GENOTYPE/expressing ATM shRNA
ZBED3 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
ENOX1 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
PRUNE2 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
SHISA5 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
BMP2 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
DCN DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
GPR64 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
OBSL1 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
GALNT10 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
PPP2R2B UP in 'expressing ATM shRNA' vs 'expressing LacZ'
EFHD2 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
GDA DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
AGPAT3 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
PRMT8 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
Analysis of 'expressing ATM shRNA' vs 'expressing LacZ'
VGLL1 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
TMPRSS13 UP in 'expressing ATM shRNA' vs 'expressing LacZ'
S100A9 DOWN in 'expressing ATM shRNA' vs 'expressing LacZ'
(Sample) cell type/isogenic hTERT-immortalized normal human mammary epithelial cell
isogenic hTERT-immortalized normal human mammary epithelial cell