A Method of Utrophin Up-regulation Through RNAi-mediated Knockdown of the Transcription Factor EN1

作者：Wang, Q.; Cao, D-H; Jin, C-L^*; Lin, C-K; Ma, H-W; Wu, Y-Y

来源：Journal of International Medical Research, 2011, 39(1): 161-171.

DOI：10.1177/147323001103900117

• DUCHENNE MUSCULAR DYSTROPHY
• UTROPHIN
• PROMOTER
• EN1
• RNA INTERFERENCE
• UP-REGULATION

The aim of this study was to induce up-regulation of the dystrophin-related gene UTRN that encodes the protein utrophin, to determine whether this could compensate for the lack of dystrophin function in Duchenne muscular dystrophy. The human UTRN promoter, which contains two putative binding sites for homeobox protein engrailed-1 (EN1), was analysed. It was found that EN1 binding site 2 in the UTRN gene promoter directly interacted with transcription factor EN1 in vitro. Chromatin immunoprecipitation assays of the EN1 UTRN promoter complex from rhabdomyosarcoma and He La cell lines confirmed that endogenous EN1 interacted with this region in vivo. The findings suggest that EN1 directly interacts with the UTRN promoter. Small interfering RNA was used to inhibit EN1 gene expression. Higher utrophin mRNA levels were observed in EN1-inhibited cells compared with controls. The increase in utrophin mRNA in rhabdomyosarcoma cells and He La cells may have resulted from inhibition of EN1 expression.

• 出版日期2011-2
• 单位中国人民解放军第二O二医院; 中国医科大学