RELA Ablation Contributes to Progression of Hepatocellular Carcinoma with TP53^R249S Mutation and is a Potential Therapeutic Target.

ABSTRACT: TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53^R249S overexpression (MT-PHHs) is performed in xenografts. The screen identified RELA as one of the most significant genes, besides NF2 and CSK, two known tumor suppressor genes (TSG) in HCC. Ablation of RELA increased the expression of genes related to cell cycling and stemness in MT-PHHs, and induced PHHs to transform into HCC in situ in Fah-deficient immunodeficient mice. Additionally, loss of RELA facilitated HCC metastasis via Epithelial-Mesenchymal Tra

SUBMITTER: Wu Z 

PROVIDER: S-EPMC12752641 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature