Ubiquitination-Dependent LLGL2 Degradation Drives Colorectal Cancer Progression via THBS3 mRNA Stabilization.

ABSTRACT: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide is highly associated with distant organ metastasis. Lethal(2) giant larvae protein homolog 2 (LLGL2) is often dysregulated in various tumors; however, the pathogenesis of CRC remains unclean. This study highlighted the tumor suppressor function of LLGL2 in CRC. Depleted LLGL2 exhibits the pro-CRC effects. RNA sequencing reveals that LLGL2 suppresses CRC progression by inhibiting the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB)/Akt pathway. Further analysis using RNA immunoprecipitation sequencing and shotgun mass spectrometry indicated that LLGL2 primarily regulates the stability of thrombospondin 3 (THBS3) mRNA by interacting with CCR4-NOT transcription complex subunit 1 (CNOT1), thus ina

SUBMITTER: Huang J 

PROVIDER: S-EPMC12533200 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature