siRNA Delivery for Control of Cyclin D1 and E2F1 Expression in Crohn's Disease

siRNA 递送用于控制克罗恩氏病中的细胞周期蛋白 D1 和 E2F1 表达

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作者:Ilaria Russo, Albino Carrizzo, Sabrina Bochicchio, Ornella Piazza, Gaetano Lamberti, Anna Angela Barba, Carmine Vecchione, Pio Zeppa, Paola Iovino, Cristina Bucci, Antonella Santonicola, Carolina Ciacci

Abstract

Evidence in inflammatory bowel diseases (IBD) supports a connection between inflammation and cancer due to the alteration of the cell cycle with loss of control at the G1/S checkpoint. In this study, we analyze the expression and modulation of CyD1 and E2F1 in colon explants from Crohn's disease (CD) patients. We used ex vivo culture of colon explants from 4 CD patients and 2 healthy controls, stimulated with lipopolysaccharide from Escherichia Coli (EC-LPS). Commercial siRNAs for CyD1 and E2F1 inhibition were encapsulated in Invivofectamine® and in purposely produced nanoliposomal vectors to silencing CyD1 and E2F1 expression. Western blot analysis was used to investigate the effect of siRNA on CyD1, E2F1 and cyclooxygenase 2 (COX-2) expression. In CD patients colon explants, CyD1 and E2F1 increased after the inflammatory stimulus but siRNA silencing attenuated their expression and controlled the COX-2 expression too. These data represent a prelimiary exploration of in vitro siRNA use.

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