YEATS Domain Containing 4 Promotes Gastric Cancer Cell Proliferation and Mediates Tumor Progression via Activating the Wnt/β-Catenin Signaling Pathway

Abstract

Increased expression of YEATS domain containing 4 (YEATS4) has been reported to have a correlation with progression in many types of cancer. However, the mechanism by which it promotes the development of gastric cancer (GC) is rarely reported. This study aimed to investigate the effect of YEATS4 on cell proliferation and tumor progression. The mRNA and protein expressions of YEATS4 in GC tissues and cell lines were analyzed. BGC-823 cells then overexpressed or silenced YEATS4 by transfection of different plasmids. The regulatory effect of YEATS on cell viability, colony formation, cell apoptosis, and tumor growth in vivo was evaluated. Finally, we explored the underlying regulatory mechanism of YEATS4 on the Wnt/β-catenin pathway. YEATS4 was highly expressed in GC tissues and cell lines. Furthermore, Kaplan‐Meier survival analysis and qRT-PCR analysis showed that the increased expression of YEATS4 indicated poor prognosis and tumor progression. The overexpression of YEATS4 significantly promoted cell proliferation and inhibited cell apoptosis, whereas the opposite trends were found upon the downregulation of YEATS4. Western blot analysis showed that the downregulation of YEATS4 inhibited protein expression and phosphorylation of β-catenin. In addition, decreased expressions of c-Myc, CDK6, CDK4, cyclin D1, and Bcl-2 and increased expression of Bax were observed in YEATS4 knockdown cells. Our results showed that increased expression of YEATS4 might play a critical role in promoting GC cell proliferation and apoptosis by activating the Wnt/β-catenin signaling pathway, indicating that the control of YEATS4 expression might be used as a promising therapy for GC.