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| Status |
Public on Jan 15, 2024 |
| Title |
A novel regulator of the PI3K/AKT pathway encoded by circ-PDE5A inhibits esophageal squamous carcinoma progression by promoting USP14-mediated deubiquitination of PIK3IP1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
To explore the specific mechanism by which circ-PDE5A affects the biological function of ESCC, we constructed KYSE30 cells with stable overexpression of circ-PDE5A and performed RNA-sequencing analysis.
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| Contributor(s) |
Lei K, Liang R, Liang J, Wang M |
| Citation(s) |
38658954 |
| |
| Submission date |
Dec 15, 2023 |
| Last update date |
May 10, 2024 |
| Contact name |
kai lei |
| E-mail(s) |
[email protected]
|
| Organization name |
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
|
| Department |
Department of Thoracic Surgery
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| Street address |
107 Yan Jiang West Road
|
| City |
Guangzhou |
| ZIP/Postal code |
510120 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1053364 |
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