DDX24 Promotes Lymphangiogenesis and Lymph Node Metastasis via AGRN Production in Cervical Squamous Cell Carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229910 | GEO | 2024/07/17
REPOSITORIES: GEO
Similar Datasets
Project description:DDX24 Promotes Lymphangiogenesis and Lymph Node Metastasis via AGRN Production in Cervical Squamous Cell Carcinoma
| PRJNA956573 | ENA
Project description:Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
| S-EPMC9124199 | biostudies-literature
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.
2021-01-29 | PXD022650 | Pride
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: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:The formation of new lymphatic vessels, or lymphangiogenesis, is a critical step of the tissue repair program. In pathological conditions involving chronic inflammation or tumorigenesis, this process is often dysregulated and can contribute to disease progression. Yet, lymphangiogenesis is still incompletely understood. In this study, we identified A2a adenosinergic signaling as an important regulator of inflammatory and tumor-associated lymphangiogenesis. Using Adora2a (A2a)-deficient mice, we demonstrated that A2a signaling was involved in the formation of new lymphatic vessels in the context of peritoneal inflammation. We also demonstrated that tumor-associated and sentinel lymph node lymphangiogenesis were impaired in A2a-deficient mice, protecting them from lymph node metastasis. Notably, A2a signaling in both hematopoietic and non-hematopoietic cells contributed to sentinel lymph node metastasis. In A2a-deficient tumor-draining lymph nodes, impaired lymphangiogenesis was associated with a reduced accumulation of B cells and decreased VEGF-C levels. Supporting a role for non-hematopoietic A2a signaling, we observed that primary murine lymphatic endothelial cells (LEC) predominantly expressed A2a receptor and that A2a signaling blockade altered LEC capillary tube formation in vitro. Finally, we observed that Adora2a, Nt5e and Entpd1 gene expression positively correlated with Lyve1, Pdpn and Vegfc in several human cancers, thereby supporting the notion that adenosine production and A2a receptor activation might promote lymphangiogenesis in human tumors. In conclusion, our study highlights a novel pathway regulating lymphangiogenesis and further supports the use of A2a or adenosine blocking agents to inhibit pathological lymphangiogenesis in cancers and block the dissemination of tumor cells through the lymphatic system.
| S-EPMC6682371 | biostudies-literature
Project description:DDX24 Mutations Associated with Vascular Malformations
2018-07-17 | GSE117133 | GEO
Project description:Purpose: The rediscovery of meningeal lymphatic vessels (MLVs) suggests a potential linkage between brain tumors and cervical lymph nodes (LNs). In this study, we investigated whether and how meningeal lymphatics regulate the metastasis of brain tumor cells. Experimental Design: We first examined the pattern of MLVs and LNs after tumor cells were injected into the cisterna magna (i.c.m.) or subdural space of mice. The meninges were isolated and analyzed by whole-mount immunofluorescence staining. LN metastasis was analyzed by detecting GFP+ tumor cells. Then we used inducible knock-out mice and AAV-VEGF-C delivery system to study the function of MLVs in mediating the metastasis of brain tumor cells. Finally, RNA-seq was used to determine the expression profiles of meningeal lymphatic endothelial cells (mLECs) in mice with or without tumors. The roles of the endothelial nitric oxide synthetase (eNOS) were evaluated both genetically and pharmacologically in vivo. Results: Meningeal lymphangiogenesis induced by GL261 and B16 tumors was correlated with dCLN swelling and metastasis. dCLN metastasis was suppressed in MLV-defective mice, while promoted in AAV-VEGF-C-treated mice. In addition, we found that VEGF-C/VEGFR3 signaling regulated both meningeal and tumor lymphangiogenesis. Tumor-associated mLECs have a distinct transcriptomic signature, which highly express eNOS. Furthermore, genetic or pharmacological inhibition of eNOS significantly suppressed meningeal lymphangiogenesis and dCLN metastasis. Conclusions: The meningeal lymphatic vasculature mediates the metastasis of brain tumors to cervical LNs, mainly through a VEGF-C/VEGFR3-eNOS signaling pathway, suggesting that MLV may be a potential therapeutic target for the extracranial metastasis of brain tumors.
2020-03-16 | GSE128207 | GEO