Expression of Sam68 Correlates With Cell Proliferation and Survival in Epithelial Ovarian Cancer.

Abstract

Src associated in mitosis, 68 kDa (Sam68) is a KH domain RNA-binding protein that belongs to the signal transduction and activation of RNA family. It is a multifunctional protein known to regulate cellular signal transduction, transcription, RNA metabolism, proliferation, and apoptosis, thus implicated in tumor growth. Herein, we investigated the clinical significance of Sam68 in human epithelial ovarian cancer (EOC). Western blot and immunohistochemical staining demonstrated that Sam68 expression was upregulated in EOC tissues and cell lines. Statistical analysis showed that high expression of Sam68 correlated with poor prognosis of patients with EOC. In vitro, serum starvation-refeeding experiment was primarily performed to confirm that Sam68 participated in the cell cycle progression of EOC cell lines. Then knocking down Sam68 level with small interfering RNA, cell cycle was arrested at G1 phase and cell proliferation impaired. Furthermore, we demonstrated that the antiproliferative effect of silencing Sam68 in EOC cells was associated with the upregulation of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, along with the downregulation of p-FOXO3a, p-Akt, and p-GSK-3β. Taken together, our findings uncovered that Sam68 played an important role in promoting the proliferation of human ovarian cancer, thereby might be a novel therapeutic target for EOC.