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E-GEOD-35525

ABSTRACT: Pivotal role of HMGA1 gene signature in highly metastatic breast cancer

OTHER RELATED OMICS DATASETS IN: PRJNA152247

PROVIDER: E-GEOD-35525 | ExpressionAtlas | 2025-01-24

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-GEOD-35525-analysis-methods.tsv	Tabular
	E-GEOD-35525-atlasExperimentSummary.Rdata	Rdata
	E-GEOD-35525-configuration.xml	Xml
	E-GEOD-35525-percentile-ranks.tsv	Tabular
	E-GEOD-35525.condensed-sdrf.tsv	Tabular

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Project description:Pivotal role of HMGA1 gene signature in highly metastatic breast cancer

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Project description:Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231) by reprogramming cancer cells to a stem-like state. We discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy. HMGA1 was knocked-down in MDA-MB-231 cells using siRNA as we previously described (Tesfaye A 2007). RNA from three independent knockdown experiements along with 3 control populations were collected by Rneasy miniprep (Qiagen) and analyzed by Affymetrix Human Exon 1.0 ST platform.

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Pivotal role of HMGA1 gene signature in highly metastatic breast cancer

Project description:Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells. MDA-MB-231 cells were transfected with HMGA1-specific siRNA or a control siRNA. Transfections were performed by using Lipofectamin RNAiMAX (Invitrogen) according to the manufacturer's procedure. Seventy-two hours after transfection, samples were processed for total RNA extraction and hybridization on Affymetrix microarrays. Four biological replicas (A, B, C, D) were used for each of the two conditions, for a total of 8 samples.

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Project description:HMGA1 is a well-established oncogene and is a master regulator in breast cancer cells controlling the shift from a non-tumorigenic epithelial-like phenotype towards a highly aggressive mesenchymal-like one. In this work we compared HMGA1-silenced versus control MDA-MB-231 by means of a label free shotgun proteomics approach and crossed these data with DNA microarray expression profile obtained on the same cells. Resulting data were then filtered for genes linked to poor prognosis in breast cancer gene expression meta-datasets. This workflow allows us to establish a small molecular signature composed by 21 members with a prognostic value as regards overall-, recurrence free-, and distant metastasis free-survival in breast cancer.

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