Similar Datasets
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.
2020-02-21 | GSE145635 | GEO
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.
2020-02-21 | GSE145632 | GEO
Project description:RFX8-mediated Transcriptional Activation of DDX24 Promotes Hepatocellular Carcinoma Via LAMB1/SRC Signaling
| PRJNA607774 | ENA
Project description:RFX8-mediated Transcriptional Activation of DDX24 Promotes Hepatocellular Carcinoma Via LAMB1/SRC Signaling [RNA-seq]
| PRJNA607778 | ENA
Project description:RFX8-mediated Transcriptional Activation of DDX24 Promotes Hepatocellular Carcinoma Via LAMB1/SRC Signaling [RIP-seq]
| PRJNA607779 | ENA
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.
2021-01-29 | PXD023321 | Pride
Project description:BackgroundMetastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood.MethodsBy performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis.ResultsGain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7.ConclusionsTaken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.
| S-EPMC10851485 | biostudies-literature
Project description:Background and aimsAccumulating studies identified that BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is integrally involved in the initiation and development of tumors. Nevertheless, the precise biological role and underlying mechanisms of BUB1B in hepatocellular carcinoma (HCC) remain indistinct.MethodTo figure out the role of BUB1B in HCC, we first assessed its expression using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then verified BUB1B expression in HCC tissues, nontumor tissues, and HCC cell lines through western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. To explore the specific function of BUB1B in HCC in vivo and in vitro, we performed the flow cytometry, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, colony formation, Transwell, wound-healing, subcutaneous tumor growth, and metastasis assays. Additionally, we identified the BUB1B-regulated pathways involved in HCC by using gene set enrichment analysis.ResultsOur data displayed that higher BUB1B expression was detected in HCC tissues and HCC cell lines. The overexpression of BUB1B was positively correlated with adverse clinicopathological characteristics. Survival analyses showed that lower recurrence-free and overall survival rates were correlated with the overexpression of BUB1B in patients with HCC. Moreover, the malignancy of HCC was facilitated by BUB1B both in vivo and in vitro. Lastly, the results were confirmed by western blots, which showed that BUB1B upregulated mTORC1 signaling pathway in HCC. Meanwhile, the oncogenic effect of BUB1B will be impaired when the mTORC1 signaling pathway was inhibited by rapamycin.ConclusionWe highlighted that BUB1B played an oncogenic role in HCC and was identified as a possible clinical prognostic factor and a potential novel therapeutic target for HCC.
| S-EPMC7643650 | biostudies-literature
Project description:The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was positively correlated with large tumor size, tumor multiplicity, late tumor-node-metastasis (TNM) stage and poor prognosis. Additional, gain-of-function and loss-of-function experimental results revealed that DDX11 overexpression promoted HCC cell proliferation, migration, invasion and inhibited cell apoptosis in vitro. Overexpression of DDX11 also enhanced HCC tumorigenicity in vivo. Furthermore, DDX11 was transcriptionally regulated by transcription factor E2F1 in HCC, as demonstrated by chromatin immunoprecipitation (Ch-IP) and luciferase reporter assays. Mechanistically, E2F1/DDX11 axis promoted HCC cell proliferation, migration and invasion, at least in part, through activating PI3K/AKT/mTOR signaling pathway. Conclusively, our study demonstrates that E2F1-enhanced DDX11 expression promotes HCC progression through PI3K/AKT/mTOR pathway and DDX11 might be a potential therapeutic and prognostic target for HCC treatment.
| S-EPMC7181644 | biostudies-literature
Project description:Metastasis is considered a dynamic process in tumor development that is related to abnormal migration and invasion. Tumor cells can move as individual cells in two interconvertible modes: mesenchymal-type and amoeboid. Previously, we reported that the interaction between CD147 and Annexin II can inhibit the amoeboid movement in hepatocellular carcinoma (HCC) cells. However, the mechanism of CD147 involved in mesenchymal movement is still unclear. Notably, our results show overexpression of CD147 led to mesenchymal-type movement in HCC cells. Evidence indicated that the mesenchymal-type cell movement induced by CD147 was Src dependent, as observed by confocal microscopy and Rac1 activity assay. The phosphorylation of Src (pY416-Src) can be up-regulated by CD147, and this regulation is mediated by focal adhesion kinase (FAK). Next, we identified DOCK8 as a GEF for Rac1, a key molecule driving mesenchymal-type movement. We also found that Src promotes STAT3 phosphorylation and STAT3 facilitates DOCK8 transcription, thus enhancing DOCK8 expression and Rac1 activation. This study provides a novel mechanism of CD147 regulating mesenchymal-type movement in HCC cells.
| S-EPMC4381592 | biostudies-literature