EIF3B Promotes KRAS Gene Mutation-Driven Colon Adenocarcinoma Progression Through the TBK1 and PI3K/AKT Signaling Pathways

Abstract

Therapeutic targets involved in multiple signaling pathways offer promising treatment options for cancers driven by KRAS gene mutations (KRAS^mut). EIF3B has emerged as a potential therapeutic target for colorectal cancer (CRC). To elucidate the role of EIF3B and its interactions with potential targets in CRC, we utilized bioinformatics techniques alongside clinicopathological analyses. RNA sequencing identified signaling pathways associated with EIF3B. The expression levels of relevant genes and their associated pathways were measured using RT-qPCR and western blot analyses. RNA immunoprecipitation (RIP) confirmed the interactions between EIF3B and these specific genes. Analysis of data from The Cancer Genome Atlas (TCGA), combined with clinicopathological studies, revealed significantly elevated levels of EIF3B and TBK1 mRNA and proteins in KRAS^mut colorectal adenocarcinoma (COAD) compared to normal tissues. Silencing EIF3B inhibited the proliferation and progression of KRAS^mut COAD and disrupted the TBK1, PI3K/AKT, and JAK2/STAT3 pathways. EIF3B also regulated the translation of TBK1 and PIK3CA. Targeting EIF3B presents a novel approach to modulating various cellular signaling pathways, offering a promising therapeutic strategy for patients with KRAS^mut COAD.