A majority of the patients with advanced
prostate cancer initially respond to
androgen deprivation
therapy and
enzalutamide therapy, but eventually enter the
castration-resistant
prostate cancer (CRPC) phase. Some studies have shown that the activation of other signalling pathways in CRPC cells replaces the function of the
androgen receptor, as well as promotes cell
metastasis and progression. However, the mechanisms underlying this side effect remain unclear. The present study aims to explore the continued progression of cells after
enzalutamide resistance. Low expression of circRNA-UCK2 (circUCK2) was detected in
enzalutamide-resistant (EnzR) cells. Moreover, miR-767-5p was found to be resistant to EnzR cells when the level of circUCK2 is increased. The decrease in free miR-767-5p increases the expression of TET1
protein through the post-transcriptional regulation of
mRNA, thereby inhibiting cell invasion and proliferation. Knocking down circUCK2 in
enzalutamide-sensitive cells reduces the concentration of TET1, thereby increasing cell invasion and proliferation. A preclinical study using in vivo mouse models also showed that a high expression of circUCK2 inhibited the EnzR cell growth. Thus, this study might aid in developing a novel
therapy to better suppress the CRPC progression.