CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA657203 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12454227.fastq.gz | Fastqsanger.gz | |||
| SRR12454228.fastq.gz | Fastqsanger.gz | |||
| SRR12454229.fastq.gz | Fastqsanger.gz | |||
| SRR12454230.fastq.gz | Fastqsanger.gz |
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Project description:CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling
| PRJNA657203 | ENA
Project description:CCAAT enhancer binding proteins (CEBPs) have critical roles in the physiological and pathological processes. However, the characteristics and contributions of CEBPs in esophageal squamous cell carcinoma (ESCC) is unknown. Here, we showed that most of CEBPs (including CEBPA, CEBPB, CEBPE, CEBPG, CEBPZ) were upregulated and amplified in ESCC. Of note, high CEBPG expression is a prognostic factor for the poor survival of patients with ESCC. Moreover, the ESCC specific transcription factor TP63 activates the expression of CEBPG by directly binding to its distal enhancer. Functionally, CEBPG significantly enhances the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, CEBPG enhances the PI3K-AKT signaling pathways through directly binding to distal enhancer or/and promoter of downstream target genes, such as CCND1, MYC and CDK2 etc. These findings provide important characteristics and contributions insights into CEBPs dysregulation in ESCC and elucidate a crucial role for CEBPG in the progression of ESCC, which highlights its potential therapeutic target for patients.
2021-08-11 | GSE156257 | 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.
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Project description:Omipalisib Inhibits Esophageal Cancer Growth through PI3K/AKT/mTOR Signalling Pathway Disruption
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Project description:CCAAT/enhancer binding proteins (CEBPs, including CEBPA, CEBPB, CEBPD, CEBPE, CEBPG, and CEBPZ) play critical roles in a variety of physiological and pathological processes. However, the molecular characteristics and biological significance of CEBPs in esophageal squamous cell carcinoma (ESCC) have rarely been reported. Here, we show that most of the CEBPs are upregulated and accompanied with copy number amplifications in ESCC. Of note, high CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. Functionally, CEBPG significantly promotes the proliferation and migration of ESCC cells both in vitro and in vivo. Mechanistically, CEBPG activates the PI3K-AKT signaling pathway through directly binding to distal enhancers and/or promoters of genes involved in this pathway, including genes of CCND1, MYC, CDK2, etc. These findings provide new insights into CEBPs dysregulation in ESCC and elucidate a crucial role for CEBPG in the progression of ESCC, highlighting its potential therapeutic value for ESCC treatment.
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Project description:The fat tail of sheep is an important organ that has evolved to adapt to extreme environmental conditions. Mesenchyme homeobox 2 (MEOX2) can inhibit adipogenic differentiation of stromal vascular fractions (SVFs) isolated from ovine tail adipose tissue. However, the underlying mechanism through which MEOX2 regulates ovine adipogenesis remains unclear. Therefore, this study aims to employ RNA sequencing (RNA-seq) to explore the downstream genes regulated by MEOX2 during the adipogenic differentiation of ovine SVFs. Based on RNA sequencing, several differentially expressed genes (DEGs) were identified in response to MEOX2 overexpression. The PI3K/AKT signaling pathway was significantly enriched in DEGs, indicating its importance in mediating fat accumulation regulated by MEOX2. Additionally, the PI3K/AKT signaling pathway activation was found to be crucial for ovine SVF adipogenic differentiation. Mechanistically, MEOX2 inhibited the PI3K/AKT pathway. These findings highlight the significance of the PI3K/AKT signaling pathway during ovine SVF adipogenic differentiation. Furthermore, they shed light on the involvement of MEOX2 in this differentiation via the PI3K/AKT pathway. Our findings provide novel insights into the critical role of MEOX2 as an adipogenetic differentiation regulator, potentially enhancing our understanding of ovine fat development and its regulatory processes.
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Project description:Esophageal squamous cell carcinoma (OSCC) is a lethal digestive tract malignancy with limited effective interventions. This study aims to explore a new potential inhibitor on OSCC and investigate the underlying mechanisms. Based on a drug screen of an FDA-proven library consisting of 1404 compounds, we demonstrated that Omipalisib, a dual PI3K/mTOR inhibitor, markedly inhibited cell proliferation and colony formation in a panel of OSCC cell lines. Mechanistically, Omipalisib induced G0/G1 phase cell cycle arrest and apoptosis. Moreover, RNA-seq, KEGG and GSEA confirmed that the PI3K/mTOR signalling pathway is the primary target of Omipalisib in OSCC cells. Omipalisib treatment suppressed the PI3K/mTOR signalling pathway. Furthermore, Omipalisib exerted a significant antineoplastic effect on OSCC tumour xenografts in BALB/c nude mice without obvious side effects. The present study supports the rationale for using Omipalisib as a therapeutic approach for OSCC cases and suggests the potential clinical evaluation of this strategy.
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Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.
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