AKT1^E17K-Interacting lncRNA SVIL-AS1 Promotes AKT1 Oncogenic Functions by Preferentially Blocking AKT1^E17K Dephosphorylation.

ABSTRACT: AKT1^E17K is a gain-of-function mutation that constitutively activates the PI3K-AKT pathway. However, how AKT1^E17K is regulated in cancer pathogenesis remains elusive. Here, RNA immunoprecipitation sequencing (RIP-seq) is performed to interrogate the AKT1^E17K-interacting lncRNAs and identify that SVIL-AS1 preferentially binds to AKT1^E17K rather than AKT1^WT proteins. It is found that SVIL-AS1 enhances AKT1 phosphorylation and downstream signaling. SVIL-AS1 knockdown dramatically inhibits the growth of AKT1^E17K cells in vitro and in vivo. Notably, AKT1 and SVIL-AS1 interaction is AKT1 phosphorylation-dependent. SVIL-AS1 also interacts with PPP2R2A, a subunit of phosphatase PP2A holoenzyme, and blocks the binding of PPP2R2A to A

SUBMITTER: Wang J 

PROVIDER: S-EPMC12097031 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature