Role of PPP2R1A in Regulation of Cell Proliferation in HeLa Cells

Abstract

Objective: PPP2R1A is a conserved subunit of protein phosphatase 2 (PP2A) and a serine/threonine phosphatase that participates in the dephosphorylation of specific proteins. Previous studies found that PPP2R1A acts as a tumor suppressor. Apart from its phosphorylation function, the specific regulatory mechanism for cancer development through PPP2R1A-mediated transcriptional or post-transcriptional regulation remains unknown. We expected to reveal potential function of PPP2R1A in cells lines. Methods: We cloned and overexpressed PPP2R1A to explore the function and regulatory pattern of PPP2R1A in HeLa cells and used RNA sequencing to analyze PPP2R1A-regulated gene expression as well as alternative splicing (AS) among PPP2R1A overexpressing cells and control cells. Results: When compared with the control samples, the overexpression of PPP2R1A resulted in a significant suppression of the proliferation in HeLa cells. Furthermore, it regulated the expression of hundreds of genes in terms of cell adhesion, positive regulation of JUN kinase activity, viral response, cell growth regulation, and positive regulation of inflammatory response. Moreover, the AS of genes involved in the cell cycle, junction adherence, endometrial cancer, and RNA transport were regulated by PPP2R1A. The genes related to tumor metastasis and AS (alternative splicing) genes were verified by quantitative reverse transcription realtime polymerase chain reaction (RT-qPCR) experiments. Conclusions: Our findings suggest that PPP2R1A may have a wide range of regulatory functions at the gene expression and post-transcriptional levels via the modulation of AS and messenger ribonucleic acid (mRNA) associated with cancer.