TNFAIP8 promotes cell growth by regulating the Hippo pathway in epithelial ovarian cancer.

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an independent prognostic factor for cancer-specific and disease-free survival in patients with epithelial ovarian cancer (EOC). However, the exact mechanism of the biological role of TNFAIP8 in EOC remains unclear. In the present study, a siRNA specifically targeting TNFAIP8 was prepared to knock down TNFAIP8 in EOC cells. Cell growth, colony formation, apoptosis, and cell cycle distribution in TNFAIP8-deficient EOC cells were determined. In addition, the underlying molecular mechanisms were investigated by western blot analysis and reverse transcription quantitative polymerase chain reaction assays. It was demonstrated that the knockdown of TNFAIP8 inhibited EOC cell growth and colony formation, along with increased levels of apoptosis and cell cycle arrest. The results of the western blot analysis suggested that TNFAIP8 inhibited the expression of phosphorylated yes-associated protein 1 (YAP) while promoting total and nuclear YAP expression, followed by the regulation of apoptosis and cell cycle checkpoint protein expression in EOC. Overexpression of YAP in EOC cells efficiently attenuated cell growth inhibition in TNFAIP8-deficient EOC cells. In addition, knockdown of TNFAIP8 significantly impaired EOC tumor growth in vivo. Collectively, the data from the present study suggested that TNFAIP8 is an oncogene and a novel therapeutic target for EOC.