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- W2045743048 endingPage "1692" @default.
- W2045743048 startingPage "1678" @default.
- W2045743048 abstract "Macrophage immigration inhibitory factor (MIF) is a ubiquitously expressed proinflammatory mediator that has also been implicated in cell growth, cell cycle and carcinogenesis. In this study, we demonstrate siRNA-mediated knockdown of MIF results in G(0)/G(1) cell cycle arrest in HEK293 cells. To elucidate the molecular mechanism of cell cycle perturbation following MIF knockdown, we employed microarray to investigate the genome-wide expression profile in MIF-deficient cells and normal cells. Quantitative real-time PCR were used to confirm the differential expression patterns of approximately 50 transcripts involved in cell cycle and signaling identified by microarray. The dynamic model of MIF-dependent signaling pathways linked to cell cycle machinery were constructed through analyzing gene expression data in the context of known biological pathways. The results demonstrate that knockdown of MIF could inhibit G(1)/S transition through inhibition of MAPK, PI3K/Akt, NFkappaB, c-Myc-dependent pathway and activation of TGFbeta, p53-dependent pathway. Meanwhile, inhibition of E2F-, NFkappaB, c-Myc and Ap-1-mediated transcription and stimulation of p53 and FoxO4 transcriptional activity will lead to differential expression of cell cycle regulators and subsequent cell cycle arrest in G(0)/G(1) phase in MIF-knockdown cells. This study provides novel insights into the pleiotropic activities of endogenous MIF, especially its essential and crucial role in cell proliferation and the cell cycle." @default.
- W2045743048 created "2016-06-24" @default.
- W2045743048 creator A5007368418 @default.
- W2045743048 creator A5053799011 @default.
- W2045743048 creator A5057837748 @default.
- W2045743048 creator A5062528871 @default.
- W2045743048 creator A5064871720 @default.
- W2045743048 creator A5068599064 @default.
- W2045743048 creator A5077583743 @default.
- W2045743048 creator A5081598925 @default.
- W2045743048 date "2008-06-01" @default.
- W2045743048 modified "2023-10-13" @default.
- W2045743048 title "A global genomic view of MIF knockdown-mediated cell cycle arrest" @default.
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