Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 3|pp 2777—2797

TP53/miR-34a-associated signaling targets SERPINE1 expression in human pancreatic cancer

Shaw M. Akula1, Peter P. Ruvolo2, James A. McCubrey1
  • 1Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834,USA
  • 2Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Received: December 4, 2019Accepted: January 12, 2020Published: January 27, 2020
https://doi.org/10.18632/aging.102776

Copyright: © 2020 Akula 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

Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.