CD95L mRNA is toxic to cells [SmallRNA_CD95L.50hrs.Drosha_ko]

>80% of a large number of tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death that is characterized by the simultaneous activation of multiple death pathways and preferentially affects transformed and cancer stem cells. We now show that these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect. We also provide evidence showing that the full length CD95L mRNA is also toxic and produces small Ago-associated RNAs. Overall design: Examination of differential gene mRNA expression in empty vector control cells versus cells over-expressing CD95L mRNA.

针对CD95或CD95配体（CD95L）的大量受试小干扰RNA（small interfering RNA, siRNA）与短发夹RNA（short hairpin RNA, shRNA）中，有80%可诱导一种细胞死亡表型：该表型以同时激活多条死亡通路为特征，并优先作用于转化细胞与癌症干细胞。本研究证实，此类si/shRNA可通过经典RNA干扰（RNA interference, RNAi）途径杀伤癌细胞，其机制为靶向关键存活基因的3'非翻译区（3' untranslated region, 3'UTR），并通过一种独特的脱靶效应发挥功能。本研究同时提供证据表明，全长CD95L mRNA同样具有细胞毒性，并可产生小型Ago结合RNA。整体实验设计：对比空载载体对照细胞与过表达CD95L mRNA的细胞之间的基因mRNA表达差异。