Image_2_Circular RNA_PDHX Promotes the Proliferation and Invasion of Prostate Cancer by Sponging MiR-378a-3p.TIF

The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence in situ hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score (P = 0.001) and pathogenic T stage (P = 0.01) and acted as an independent prognostic factor of poor survival (P = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion in vitro and in vivo, but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.