ArticleJournal of experimental & clinical cancer research : CR2024
CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- The role of deubiquitinating enzymes and their inhibitors in esophageal carcinoma (Review).International journal of oncology · 2026Review
- Review
- Tumor-Derived Exosomal circAP2B1 Induces M2 Macrophage Polarization by Enhancing Mitochondrial Homeostasis to Promote Esophageal Squamous Cell Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- Targeting circGDI2 disrupt HNRNPC-mediated mPORCN stabilization and enhance LGK-974 anti-tumor therapy in hepatocellular carcinoma.Molecular cancer · 2026Article
- Advances in epigenetic therapy for esophageal cancer.Clinical epigenetics · 2026Review
- Circular RNAs: Fundamental mechanisms in tumor metastasis and detection strategies (Review).Molecular medicine reports · 2025Review
- Recent advances of circular RNAs in gastrointestinal cancer.World journal of clinical oncology · 2025Review
- A circRNA promotes esophageal squamous cell carcinoma progression by inhibiting TRIM25-mediated degradation of IGF2BP family members.Molecular cancer · 2025Article
- Integrating network pharmacology and molecular modeling to decipher the anti-esophageal squamous cell carcinoma mechanisms of Bidens pilosa L.Discover oncology · 2025Article
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- EIF4A3-induced circPRKAR1B promotes esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB induced CCL3 secretion.Cancer cell international · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Significance of circular RNAs in regulating protein ubiquitination for malignant tumor progression.Frontiers in immunology · 2025Review
- Circ_0096710 facilitates tumor growth via controlling ADAM10 expression in esophageal squamous cell carcinoma.Thoracic cancer · 2025Article
- The Dual Roles of Circular RNAs in Breast Cancer Distant Metastasis and Their Clinical Applications.Journal of Cancer · 2025Review
- Unlocking ESCC Progression: CCL15-CCR1 Axis Activates AKT/ERK1/2/c-Jun/CDK2 Pathway.Journal of Cancer · 2025Article
- Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.MedComm · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. 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 the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC.
methodsDifferential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC-MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A.
resultsWe found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S-S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo.
conclusionThe novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.