Molecular Carcinogenesis

Funding information National Natural Science Foundation of China, Grant/Award Numbers: No. 81272957, No.81472520 and No.81502354; the National Science Foundation of China, Grant/Award Numbers: 81472520, 81600880, 81502354; Qingdao/China Postdoctoral Science Foundation, Grant/Award Numbers: 2017M612217, 2017M622145; Source Innovation Planning of Qingdao, Grant/Award Numbers: 17‐1‐1‐42‐jch, 18‐2‐2‐77‐jch, 17‐ 1‐1‐45‐jch; Natural Science Foundation of Shaanxi/Shandong Province, Grant/Award Numbers: ZR2018BH021, 2016JQ8028, 2015JM8396, 2017WS215 Abstract Recent findings have shown that dysregulation of circular RNAs (circRNAs) is implicated in various cancers. However, the contribution of circRNAs in oral squamous cell carcinoma (OSCC) remains largely unexplored. We screened circRNA expression profiles using a circRNA microarray in paired OSCC and normal tissues and explored the clinical significance of a downregulated circRNA, circ‐PKD2. Moreover, the biological function of circ‐PKD2 in OSCC was investigated both in vitro and in vivo. We found that downregulation of circ‐PKD2 in OSCC correlated significantly with aggressive characteristics. Further analysis revealed that overexpression of circ‐PKD2 inhibited OSCC cell proliferation, migration and invasion, induced apoptosis and cell cycle arrest, which were promoted by knockdown of circ‐ PKD2. In addition, circ‐PKD2 was identified as a sponge for miR‐204‐3p and upregulated the expression of adenomatous polyposis coli 2 (APC2), which was the functional target of miR‐204‐3p. Moreover, circ‐PKD2 attenuated the oncogenic effects of miR‐204‐3p‐mediated APC2 on OSCC progression via multiple signaling pathways. These results demonstrate that the circ‐PKD2/miR‐204‐3p/APC2 axis represents a novel pathway involved in the pathogenesis of OSCC and may serve as a novel therapeutic target of OSCC.