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Updated: Oct 2, 2025

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Pseudogene AK4P1 promotes pancreatic ductal adenocarcinoma progression through relieving miR-375-mediated YAP1
Lang Jia1,2, Yun Zhang1,3, Feng Pu1,3
1Organ Transplant Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
Abstract:
Pseudogenes have been reported to play oncogenic or tumor-suppressive roles in cancer progression. However, the molecular mechanism of most pseudogenes in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, we characterized a novel pseudogene-miRNA-mRNA network associated with PDAC progression using bioinformatics analysis. After screening by dreamBase and GEPIA, 12 up-regulated and 7 down-regulated differentially expressed pseudogenes (DEPs) were identified. According to survival analysis, only elevated AK4P1 indicated a poor prognosis for PDAC patients. Moreover, we found that AK4 acts as a cognate gene of AK4P1 and also predicts worse survival for PDAC patients. Furthermore, 32 miRNAs were predicted to bind to AK4P1 by starBase, among which miR-375 was identified as the most potential binding miRNA of AK4P1. A total of 477 potential target genes of miR-375 were obtained by miRNet, in which 49 hub genes with node degree ≥ 20 were identified by STRING. Subsequent analysis for hub genes demonstrated that YAP1 may be a functional downstream target of AK4P1. To confirmed the above findings, microarray, and qRT-PCR assay revealed that YAP1 was dramatically upregulated in both PDAC cells and tissues. Functional experiments showed that knockdown of YAP1 significantly suppressed PDAC cells growth, increased apoptosis, and decreased the ability of invasion. In conclusion, amplification of AK4P1 may fuel the onset and development of PDAC by targeting YAP1 through competitively binding to miR-375, and serve as a promising biomarker and therapeutic target for PDAC.
Insights
Pseudogene AK4P1 promotes pancreatic cancer by interacting with miR-375 and upregulating YAP1. This AK4P1-miR-375-YAP1 axis offers a potential therapeutic target for pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Pseudogenes can influence cancer progression, but their roles in pancreatic ductal adenocarcinoma (PDAC) are largely uncharacterized.
- Understanding pseudogene functions is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the molecular mechanisms of pseudogenes in PDAC progression.
- To identify a novel pseudogene-miRNA-mRNA network associated with PDAC.
Main Methods:
- Bioinformatic analysis using dreamBase, GEPIA, starBase, miRNet, and STRING databases.
- Survival analysis to correlate pseudogene expression with patient prognosis.
- Microarray and qRT-PCR assays to validate gene expression.
- Functional experiments (e.g., gene knockdown) to assess YAP1's role in PDAC.
Main Results:
- Identified 12 upregulated and 7 downregulated differentially expressed pseudogenes (DEPs) in PDAC.
- Elevated AK4P1 expression was associated with poor prognosis in PDAC patients.
- Established a network where AK4P1 targets YAP1 by competitively binding to miR-375.
- YAP1 upregulation was confirmed in PDAC tissues, and its knockdown inhibited tumor growth, invasion, and promoted apoptosis.
Conclusions:
- AK4P1 amplification drives PDAC development by modulating the AK4P1-miR-375-YAP1 axis.
- AK4P1 represents a potential biomarker and therapeutic target for PDAC.
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