Search results for "off-target effect"

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Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform

2017

Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-Δe8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a specific siRNA that spares the Hipk2-Δe8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant-negative effect of Hipk2-FL over the Δe8 isoform. From this observation, we sought to take advantage and assessed the therape…

0301 basic medicineGene isoformMaleProgrammed cell deathSmall interfering RNACell SurvivalBlotting WesternMice Nudecolorectal cancerApoptosisHIPK2BiologyProtein Serine-Threonine KinasesGene Expression Regulation Enzymologic03 medical and health sciencesExonRNA interferenceCell Line TumorAnimalsHumansViability assayoff-target effectCell Line TransformedSettore MED/04 - Patologia GeneraleKinaseReverse Transcriptase Polymerase Chain ReactionAlternative splicingalternative splicing isoformoff-target effectsExonsHCT116 CellsMolecular biologyXenograft Model Antitumor AssaysCell biologyGene Expression Regulation NeoplasticIsoenzymesAlternative Splicing030104 developmental biologyRNAi TherapeuticsOncologyalternative splicing isoformsNeoplastic Stem CellsRNA InterferenceHIPK2; alternative splicing isoforms; colorectal cancer; off-target effects; siRNA therapeutic applicationsiRNA therapeutic applicationCarrier ProteinsColorectal NeoplasmsGene DeletionResearch Paper
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