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.

Aging
|February 27, 2022
PubMed

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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