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| Status |
Public on Jan 15, 2024 |
| Title |
Study on the mechanism of circ-PDE5A inhibiting the progression of esophageal squamous cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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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 |
Three pairs of ESCC tissues and adjacent normal tissues were analyzed for differentially expressed circRNA using the Arraystar Human circRNA Array analysis.
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| Contributor(s) |
Lei K, Liang R, Liang J, Wang M |
| Citation(s) |
38658954 |
| |
| Submission date |
Dec 18, 2023 |
| Last update date |
May 10, 2024 |
| Contact name |
kai lei |
| E-mail(s) |
leik5@mail2.sysu.edu.cn
|
| Organization name |
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
|
| Department |
Department of Thoracic Surgery
|
| Street address |
107 Yan Jiang West Road
|
| City |
Guangzhou |
| ZIP/Postal code |
510120 |
| Country |
China |
| |
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| Platforms (1) |
| GPL21825 |
074301 Arraystar Human CircRNA microarray V2 |
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| Samples (6)
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| GSM7978792 |
Esophageal squamous cell carcinoma tissue 1 |
| GSM7978793 |
Esophageal squamous cell carcinoma tissue 2 |
| GSM7978794 |
Esophageal squamous cell carcinoma tissue 3 |
|
| Relations |
| BioProject |
PRJNA1053927 |
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