Silencing of circDPP4 suppresses cell progression of human prostate cancer and enhances docetaxel cytotoxicity through regulating the miR‐564/ZIC2 axis

Background Circular RNA derived from dipeptidyl peptidase 4 (circDPP4; ID: hsa_circ_0056881) is one of the top increased circRNAs in prostate cancer (PC) and docetaxel (DTX)‐based chemotherapy is the primary therapeutic choice for PC. However, its repertoire in PC development and chemoresistance remains to be documented. Methods Expression of circDPP4, microRNA (miR)‐564, and zinc finger of the cerebellum 2 (ZIC2) was detected by a real‐time quantitative polymerase chain reaction and western blotting; the direct interaction was validated by an RNA pull‐down assay, a dual‐luciferase reporter assay, and RNA immunoprecipitation. Cell progression was measured by a cell‐counting kit‐8 assay, colony formation assay, flow cytometry, a transwell assay, a xenograft experiment, and immunohistochemistry. DTX cytotoxicity was confirmed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) cell viability assay. Results Expression of circDPP4 is upregulated in PC tumors from 60 patients and PC cell lines, and a higher circDPP4 might predict poor overall survival. Decreasing circDPP4 suppresses cell proliferation, colony formation, migration/invasion, and 50% inhibitory concentration of DTX in PC cells, and promotes the apoptosis rate. Both overexpressing miR‐564 and inhibiting ZIC2 could imitate those effects, whereas inhibiting miR‐564 and restoring ZIC2 could separately counteract them. Mechanistically, circDPP4 functions as a miR‐564 sponge and regulates the expression of ZIC2, a target gene for miR‐564. Tumor growth is retarded by silencing circDPP4, accompanied by elevated miR‐564 and attenuated Ki‐67 and ZIC2. Conclusions Blocking circDPP4 antagonizes cell progression of PC and contributes to in vitro DTX cytotoxicity via regulating the miR‐564/ZIC2 axis, at least. The present study suggests that circDPP4 is a potential biomarker and target for PC. CircDPP4 sponges miR‐564 from its binding to ZIC2 in PC cells, resulting in excessive proliferation and migration/invasion and decreased apoptosis and DTX cytotoxicity.