Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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Transcriptional profiling of lung cancer cells over-expression miR-34a.


ABSTRACT: The Zeb1 transcriptional repressor plays a key role in metastasis through the down-regulation of genes that are strong inducers of epithelial differentiation and inhibitors of stem-ness. Here we report that Zeb1 controls the expression of numerous oncogenic and tumor suppressive microRNAs (miRs). Zeb1 stimulated pro-migratory cytoskeletal processes by down-regulating miR-34a and activated Rho GTPases through Arhgap1, a Cdc42 GTPase activating protein and novel miR-34a target gene. Poor-prognosis human lung adenocarcinomas were highly enriched in a cytoskeletal gene signature activated by miR-34a down-regulation. These findings suggest that Zeb1 regulates a miR network and drives pro-migratory cytoskeletal processes through miR-34a. Total RNA was extracted from primary tumors from mice injected with 344SQ-vector and -miR-34a cells, and then hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 array. Determination of differentially expressed genes was carried out.

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton 

PROVIDER: E-GEOD-38341 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression.

Ahn Young-Ho YH   Gibbons Don L DL   Chakravarti Deepavali D   Creighton Chad J CJ   Rizvi Zain H ZH   Adams Henry P HP   Pertsemlidis Alexander A   Gregory Philip A PA   Wright Josephine A JA   Goodall Gregory J GJ   Flores Elsa R ER   Kurie Jonathan M JM  

The Journal of clinical investigation 20120801 9


Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can target multiple genes with diverse functions, we posited that the prometastatic network controlled by ZEB1 extends beyond these process  ...[more]

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