Upregulated Circular RNA KIF4A Promotes Cell Migration and Invasion by Regulating MicroRNA-144-3p/EZH2 Axis in Gastric Cancer

Accumulating evidence has shown that circular RNAs (circRNAs) serve a critical regulatory role in various human cancers, including gastric cancer (GC), and in this study, we aimed to explore the functions of circKIF4A in the progression of GC. Our findings demonstrated that circKIF4A was highly expressed in both GC tissues and cell lines, and high intratumoral circKIF4A expression predicted a poor prognosis in GC patients. In vitro gain- and loss-of-function assays indicated that circKIF4A knockdown suppressed the proliferation, migration, invasion, and EMT of GC cells, while these malignant behaviors were enhanced by circKIF4A overexpression. Mechanistically, we found that circKIF4A was mainly located in the cytoplasm, could directly interact with microRNA- (miR-) 144-3p, and functions as a miRNA sponge to regulate EZH2 expression in GC cells. miR-144-3p inhibition or EZH2 restoration largely blocked the effects of circKIF4A knockdown on the malignant behaviors of GC cells. This study indicated that circKIF4A can efficiently sponge miR-144-3p to promote the malignant behaviors of GC cells and may provide a potential biomarker and therapeutic target for GC management.