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Identification of Nrf2-regulated genes in A549 lung cancer cells by oligonucleotide microarray

ABSTRACT: To elucidate the mechanisms by which Nrf2 regulates cell growth, we performed global gene expression profiling of A549 lung cancer cells with knockdown of Nrf2. Gene networks associated with carbohydrate metabolism and drug metabolism were significantly downregulated in Nrf2-depleted A549 cells. Gene Set Enrichment Analysis revealed significant enrichment of genes associated with carbohydrate catabolic processes, positive regulation of metabolic processes, PPP, and arachidonic acid metabolism. In summary, this analysis revealed that Nrf2 positively regulates transcription of genes that play key roles in central carbon metabolism. A549 cells were transfected with non targeting NS siRNA or siRNA targeting Nrf2. Mock transfected A549 cells were treated with transfection reagent alone. We had 3 biological replicates for each of the 3 groups. Ninty six hours post transfection, cells were lysed and total RNA was isolated.

ORGANISM(S): Homo sapiens

SUBMITTER: George Acquaah-Mensah 

PROVIDER: E-GEOD-38332 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and ¹³C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustain  ...[more]

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