CircTRRAP (hsa_circ_0081234) participates in prostate cancer progression and glycolysis by HOXA1 via functioning as a miR-515-5p sponge

Abstract

AbstractDysregulated circular RNAs (circRNAs) are implicated in prostate cancer (PCa) progression. Hsa_circ_0081234 (circTRRAP) has been revealed as a facilitator in PCa, but the mechanisms associated with circTRRAP in PCa progression are largely unclear. The present study was to explore the regulatory mechanism of circTRRAP-mediated PCa progression. A total of 50 PCa tissues and normal tissues were collected. RNA levels of circTRRAP, microRNA (miR)-515-5p and homeobox A1 (HOXA1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, proliferation, migration, and invasion were estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, 5-ethynyl-2ʹ-deoxyuridine (EdU) and transwell assays, respectively. Cell glycolysis was assessed by measuring glucose uptake and lactate production. The target interaction between circTRRAP or HOXA1 and miR-515-5p was investigated by the dual-luciferase reporter assay. We observed the overt upregulaiton of circTRRAP in PCa samples and cells. Silencing of circTRRAP lowered tumor growth in vivo and restrained PCa cell viability, proliferation, migration, invasion, and glycolysis in vitro. miR-515-5p was negatively regulated by circTRRAP and its deficiency reversed the inhibiting effects of circTRRAP knockdown on PCa cell malignancy and glycolysis. HOXA1 was confirmed as a miR-515-5p target and miR-515-5p overexpression lessened PCa cell malignancy and glycolysis by decreasing HOXA1 expression. Importantly, circTRRAP mediated HOXA1 expression by functioning as a miR-515-5p sponge. In conclusion, circTRRAP took part in PCa progression and glycolysis through mediating the miR-515-5p/HOXA1 axis, suggesting that circTRRAP can serve as a potential therapeutic target for PCa patients.