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J Cell Physiol. 2019 Dec 19. doi: 10.1002/jcp.29414. [Epub ahead of print]

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients.

Author information

1
Hematology/Oncology Program, Centro de Investigación Médica Aplicada (CIMA), University of Navarra, Pamplona, Spain.
2
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
3
University of Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain.
4
CIBERONC Instituto de Salud Carlos III, Madrid, Spain.
5
Biochemistry and Genetics Department, University of Navarra, Pamplona, Spain.
6
IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.

Abstract

Mesothelioma is an aggressive tumor that affects thousands of people every year. The therapeutic options for patients are limited; hence, a better understanding of mesothelioma biology is crucial to improve patient survival. To find new molecular targets and therapeutic strategies related to the protein phosphatase 2A (PP2A) network, we analyzed the gene expression of known PP2A inhibitors in mesothelioma patient samples. Our analysis disclosed a general overexpression of all PP2A-negative regulators in mesothelioma patients. Moreover, the expression of ANP32E and CIP2A genes, increased in 16% and 11% of cases, positively correlates with the ones of all the other PP2A regulators and the ones of the main cyclins and CDKs, suggesting the existence of a feed-forward loop that might contribute to the mesothelioma progression via PP2A inactivation. Overall, our study indicates the existence of a strategic and targetable axis between PP2A inhibitors (ANP32E and CIP2A) and cell cycle regulators (cyclin B2/CDK1) and provides a valuable rationale for using a personalized combinational therapy approach to improve mesothelioma patient survival.

KEYWORDS:

CDKs; PP2A; cell cycle; cyclins; data mining; gene expression; mesothelioma; therapy

PMID:
31858592
DOI:
10.1002/jcp.29414

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