Abstract

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.