Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells.

Abstract

Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has recently been reported to have an oncogenic role via the suppression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) activity, and the subsequent activation of phosphoinositide 3‑kinase (PI3K) signaling. However, the detailed role of PREX2a in osteosarcoma (OS) remains unclear. Reverse transcription quantitative polymerase chain reaction and western blotting was used to detect mRNA and protein levels. MTT assay was performed to examine cell proliferation and a Transwell assay and wound healing assay were conducted to examine cell invasion and migration. The present study demonstrated that PREX2a was markedly upregulated in OS cell lines, as compared with in normal osteoblast hFOB1.19 cells. In addition, knockdown of PREX2a expression significantly inhibited OS cell proliferation, whereas overexpression of PREX2a markedly promoted OS cell proliferation. Inhibition of PREX2a also markedly suppressed the invasion and migration of OS cells, at least partly by suppressing the protein expression of matrix metalloproteinase (MMP)2 and MMP9. Conversely, upregulation of PREX2a enhanced OS cell invasion and migration. In addition, PI3K signaling activity was significantly reduced following knockdown of PREX2a, and this was accompanied by an upregulation of PTEN activity. The results of the present study suggested that PREX2a may act as an oncogene in OS via the inhibition of PTEN activity and activation of PI3K signaling.