Circular RNAs (circRNAs) function as modulators of microRNAs (miRNAs) and are often involved in cancer progression. This study aims to investigate the underlying mechanism by which circRNA hsa-circ-000684 promotes the progression of gastric cancer (GC). Expression of hsa-circ-000684 and that of ZEB1 mRNA were elevated while microRNA-186 (miR-186) expression was downregulated in GC cell lines and clinical tissues. In addition, the effects of hsa-circ-000684 on the proliferation, migration, invasion, and tube formation of GC cells were examined through gain-and loss-of-function experiments. Furthermore, we introduced tumor xenografts into nude mice to better understand these effects in vivo. Either knockdown of hsa-circ-000684 or upregulation of miR-186 inhibited GC cell proliferation, migration, invasion, and tube formation in vitro, and reduced the xenograft tumor growth in nude mice. Moreover, we found that hsa-circ-000684 and ZEB1 directly bound to miR-186. Hsa-circ-000684 increased the expression of ZEB1 by binding to miR-186. The tumor suppressive effects of hsa-circ-000684 knockdown were reversed by inhibition of miR-186. Collectively, our data show that hsa-circ-000684 reduces the miR-186 expression which leads to an increase in the ZEB1 expression and, consequently, promotion of GC progression.
Keywords: ZEB1; angiogenesis; circular RNA hsa-circ-000684; gastric cancer; microRNA-186.
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