Project description:To investigate the role of DDX24 in vascular smooth muscle cells, RNA-seq of HUASMC/HUVSMC with DDX24 knockdown was performed. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells.
Project description:DEAD-box helicase 24 (DDX24) is a member of the DEAD-box protein family, which is essential for various aspects of RNA metabolism. DDX24 has been reported to play a role in ribosome biogenesis, transcription, and mRNA stability. Previous studies have implicated the functions of DDX24 in innate immunity, vascular malformation, cell growth, and cancer progression. Here, we describe a novel function of DDX24 in regulating the oxidative stress response and protecting cells from apoptosis. Our research revealed that DDX24 specifically regulates the expression of the heme oxygenase-1 (HO-1) gene, as determined by RNA sequencing analysis. HO-1 is responsible for degrading heme into carbon monoxide (CO), biliverdin, and ferrous ion (Fe2+), thereby exerting anti-apoptotic and anti-oxidative effects. We validated the regulation of HO-1 by DDX24 in both DDX24-depleted and DDX24-overexpressing HEK293 cells. Our findings indicate that DDX24 is involved in the induction of HO-1 expression under oxidative stress conditions. Importantly, DDX24 regulates the transcription of HO-1 instead of its mRNA stability, likely acting at the promoter and enhancer E1 region of the HO-1 gene. Furthermore, DDX24 depletion in HEK293T cells inhibits cell viability. DDX24 exerts both anti-apoptotic and anti-oxidative effects during oxidative stress. These results suggest that DDX24 plays a crucial role in protecting cells from oxidative stress-induced damage by regulating the transcription of HO-1.
Project description: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.
Project description:Accumulating evidence suggests that DEAD-box proteins are essential in RNA metabolism and play pivotal roles in cancer progression. However, the mechanisms underlying how DDX24 drives hepatocellular carcinoma (HCC) remain largely unknown. In this study, we demonstrated that DDX24 was an oncogene and identified RFX8 as a DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression.
Project description:Accumulating evidence suggests that DEAD-box proteins are essential in RNA metabolism and play pivotal roles in cancer progression. However, the mechanisms underlying how DDX24 drives hepatocellular carcinoma (HCC) remain largely unknown. In this study, we demonstrated that DDX24 was an oncogene and identified DDX24 promoted HCC development via interacting with NCL.
Project description: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.
Project description:Lung cancer remains a major global health burden with limited therapeutic options. Alternative splicing, a critical post-transcriptional process, contributes to lung cancer progression through autophagy, although the underlying mechanisms remain largely unexplored. Here we reveal that loss of DDX24, an RNA-binding protein, suppresses lung cancer growth by promoting autophagy. Mechanistically, DDX24 regulates the alternative splicing of autophagy-related genes, including IKBKG. We demonstrate that DDX24 directly binds to IKBKG pre-mRNA, whereas DDX24 ablation promotes the generation of a pro-autophagic long splicing variant. Functional rescue experiments confirm that the long IKBKG isoform-mediated autophagy confers the anti-tumor effects of DDX24 depletion. These findings uncover a novel regulatory axis involving DDX24, IKBKG splicing, and autophagy in lung cancer and provide a potential therapeutic target for this devastating disease.
