Aging
Navigate
Submit an Article
Research Paper|Volume 14, Issue 4|pp 1983—2003

Pseudogene AK4P1 promotes pancreatic ductal adenocarcinoma progression through relieving miR-375-mediated YAP1 degradation

Lang Jia1,5, Yun Zhang1,4, Feng Pu1,4, Chong Yang1,4, Shula Yang1,4, Jinze Yu1,4, Zihan Xu1,4, Hongji Yang1,2,4, Yu Zhou3,4, Shikai Zhu1,2,4
  • 1Organ Transplant Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
  • 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China
  • 3Human Disease Gene Study Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
  • 4Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
  • 5School of Clinical Medicine, Southwest Medical University, Luzhou 646000, China
* Equal contribution
Received: November 1, 2021Accepted: February 22, 2022Published: February 27, 2022
https://doi.org/10.18632/aging.203921

Copyright: © 2022 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.