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

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.

miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage

“…The ER acts as the specific cellular site of synthesis, folding, and structural maturation and trafficking of secretory and cell-surface proteins, and recent evidence showed that impaired ER homeostasis contributed to reproductive physiology and pathology including implantation and placentation, pregnancy complications and preterm birth (Guzel et al 2017). It was reported that CLN8 interacts with protein phosphatase 2A (PP2A) in human fibroblasts (Adhikari et al 2019), and as a major intracellular serine/threonine phosphatase, PP2A regulates a number of signaling pathways, including the cyclins/CDKs pathways (Lin et al 2018, Pippa et al 2020). CCNB1, CCND1 and CCNE1 have been reported to be involved in human EnSCs proliferation (Das 2009), and in the present study, decreased expression levels of these three cyclins were observed in miR-3074-5p-overexpressed T-HESC.…”

The Role of MYC and PP2A in the Initiation and Progression of Myeloid Leukemias

“…Recent reports have highlighted the role of the PP2A endogenous inhibitors ANP32A, SET, CIP2A, and ARPP19 ( Figure 2), and their role in cancer progression [85,86]. Particularly, their alterations in myeloid leukemia are reported in Table 2.…”