RFX8-mediated Transcriptional Activation of DDX24 Promotes Hepatocellular Carcinoma Via LAMB1/SRC Signaling [RIP-seq]

ABSTRACT: Hepatocellular carcinoma (HCC) is not only the fifth most prevalent cancer, presenting a major global health problem, but also among the leading causes of cancer-related deaths worldwide as its therapeutic targets are limited. To identify novel therapeutic targets, elucidate its oncogenic activities and molecular mechanism in HCC is urgent. We used R language edgeR package screened the expression profiles of 374 tissue samples obtained from patients with HCC and 50 samples of normal liver tissues obtained from The Cancer Genome Atlas (TCGA) database. Focusing on DDX24, we explored the functional effect and clinical significance of DDX24 in HCC. We provided evidence that DDX24 was a potential pro-tumorigenic gene in HCC. DDX24 knockdown inhibited HCC cell growth in vitro and in vivo. Mechanistically, RFX8 was proved to be DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression. Furthermore, we found that DDX24 bound to, and increased the stability of, LAMB1 mRNA by RNA immunoprecipitation (RIP) sequencing and RNA sequencing. Survival analysis indicated that HCC patients with high DDX24, RFX8, or LAMB1 expression exhibited poor prognosis. Our results demonstrated that DDX24 promoted HCC via RFX8/DDX24/LAMB1 pathway, which can be exploited as potential therapeutic target against HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145632 | GEO | 2020/02/21

REPOSITORIES: GEO