Background

Circular RNA derived from dipeptidyl peptidase 4 (circDPP4; ID: hsa_circ_0056881) is one top increased circRNA 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 real-time quantitative PCR and western blotting; the direct interaction was validated by RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation. Cell progression was measured by cell counting kit-8, colony formation assay, flow cytometry, Transwell assay, xenograft experiment, and immunohistochemistry. DTX cytotoxicity was confirmed by MTT cell viability assay.

Results

Expression of circDPP4 is upregulated in PC tumors from 60 patients and PC cell lines, and 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 apoptosis rate. Both overexpressing miR-564 and inhibiting ZIC2 could imitate those effects, while inhibiting miR-564 and restoring ZIC2 could separately counteract that. Mechanistically, circDPP4 functions as miR-564 sponge and regulates the expression of ZIC2, a target gene for miR-564. Tumor growth is retarded by silencing circDPP4, accompanied with elevated miR-564 and attenuated Ki-67 and ZIC2.

Conclusion

Blocking circDPP4 antagonizes cell progression of PC and contributes to in vitro DTX cytotoxicity via regulating miR-564/ZIC2 axis, at least. This study suggests circDPP4 as a potential biomarker and target for PC.