Circ-GSK3beta Promotes metastasis in esophageal squamous cell carcinoma by targeting GSK3beta to augment beta-catenin Signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA545480 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Circular RNAs, a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. We found that CircGSK3beta exerts critical roles in promoting ESCC metastasis and may serve as an exploitable therapeutic target for patients with ESCC. The plasma level of circGSK3beta have promising potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.
2019-11-25 | GSE131969 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250413 | GEO
Project description:Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The circRNA roles in esophageal squamous cell carcinoma (ESCC) is unknown. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. We then investigated the effects of the differentially expressed circRNA ARFGAP with RhoGAP domain, ankyrin repeat and PH domain 2 (circ-ARAP2) on tumor progression in vivo and in vitro. We used luciferase reporter assays to identify the relationships between circ-ARAP2, its target microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). Expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in ESCC tissues and cell lines. The circ-ARAP2 down-regulation suppressed ESCC proliferation, tumor growth and metastasis in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 slowed ESCC cell proliferation and invasion after silencing circ-ARAP2. circ-ARAP2 also influenced the endothelial-mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.
2024-07-03 | GSE179757 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250323 | GEO
Project description:Study on the mechanism of circ-PDE5A inhibiting the progression of esophageal squamous cell carcinoma
| PRJNA1053927 | ENA
Project description:We identified a number of deregulated genes through transcriptome analysis on esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues. Our pathway enrichment analysis suggested that deregulated genes were strongly enriched in multiple functionally linked pathways known to be important in tumor cell proliferation (e.g., the p53 pathway and the cell-cycle pathway) and migration (e.g., the Notch pathway, the Wnt/β-catenin pathway). To identify the functional pathways playing important roles in the tumorigenesis of esophageal squamous cell carcinoma, pooled 10 ESCC tissues and pooled 10 adjacent normal tissues were analyzed using gene expression microarrays.
2016-07-24 | E-GEOD-77531 | biostudies-arrayexpress
Project description:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The majority of GIST patients eventually develop resistance to imatinib therapy. To identify the responsible mechanisms, we investigated the differentially expressed mRNAs and circRNAs in imatinib-resistant GISTs using SBC ceRNA microarrays. We found that 107 mRNAs and 521 circRNAs were significantly differentially expressed between imatinib-naïve and imatinib-resistant GIST tissue samples. qRT-PCR analyses validated that circ-BRIP1, circ-EPHB4 and circ-RECQL4 and their host genes were upregulated in imatinib-resistant GISTs, and circ-BRIP1, circ-EPHB4, and RECQL4 were associated with imatinib resistance, tumor relapse and progression, and metastasis in GIST patients. The expression levels of circ-BRIP1, circ-EPHB4 and their host genes were also evaluated using TMAs with 150 human GISTs. The expression level of EPHB4 was significantly increased in high-grade GISTs in comparison to low-grade GISTs and correlated with imatinib resistance. Specifically, we first developed a method for high-throughput analysis of the expression of differentially expressed circRNAs by ISH-IHC in a set of FFPE-tissue microarrays in GIST. Our results also suggested a possible role for circ-BRIP1, circ-EPHB4, and their host genes in the progression of GISTs.
2024-11-01 | GSE188700 | GEO
Project description:Circular RNAs (circRNAs), a subclass of noncoding RNAs characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNAs in regulating the Wnt/β-catenin signaling and cancer progression still remain elusive. We identify one intronic circRNA derived from CTNNB1 (circ-CTNNB1) as a novel driver of cancer progression. To investigate the mechanisms underlying the oncogenic functions of circ-CTNNB1, we employed the Illumina HiSeq X Ten as a discovery platform to analyze the transcriptome profiling changes of human gastric cancer AGS cells in response to stable over-expression of circ-CTNNB1. The results showed that stable over-expression of circ-CTNNB1 led to altered expression of 2230 human mRNAs, including 1244 up-regulated genes and 986 down-regulated genes. Furthermore, we validated the RNA-seq results by real-time RT-PCR with high identity. Overall, our results provided fundamental information about the transcriptomic changes in response to circ-CTNNB1 over-expression in human cancer cells, and these findings will help us understand the pathogenesis of cancer progression.
2019-09-30 | GSE120496 | GEO
Project description:We identified a number of deregulated genes through transcriptome analysis on esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues. Our pathway enrichment analysis suggested that deregulated genes were strongly enriched in multiple functionally linked pathways known to be important in tumor cell proliferation (e.g., the p53 pathway and the cell-cycle pathway) and migration (e.g., the Notch pathway, the Wnt/β-catenin pathway).
2016-07-24 | GSE77531 | GEO
Project description:Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from a non-canonical splicing event, ubiquitously expressed among Eukaryotes and conserved among different species. We identified a circRNA (circ-ZNF609) involved in the regulation of human primary myoblast proliferation. Upon its depletion, the percentage of proliferating myoblasts was highly reduced. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in Rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is up-regulated in biopsies from both the two major RMS subtypes, the alveolar (ARMS) and the embryonal (ERMS), and we discovered that its knock-down blocks proliferation of an ERMS-derived cell line, while it has no effect on ARMS-derived cells. To understand the mechanism through which circ-ZNF609 affects cell proliferation we compared the different effects of circ-ZNF609 depletion in ERMS and ARMS and we identified genes and pathways on which the circRNA acts.
2018-12-14 | GSE117609 | GEO