Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis

Abstract

We previously reported the elevated expression of circ_0057558 in prostate cancer tissues and cell lines. Here, we aimed to determine the biological function of circ_0057558 in prostate cancer. In the current study, circ_0057558 knockdown in prostate cancer cells significantly repressed cell proliferation and colony formation, but promoted cell arrest and enhanced the sensitivity to docetaxel. Bioinformatics analysis prediction and RNA-pull down assay identified miR-206 as the potential binding miRNA of circ_0057558. A negative correlation was observed between the expression of miR-206 and circ_0057558 in prostate cancer tissues. miR-206 mimics rescued the function of circ_0057558 overexpression on prostate cancer cells. Further, the bioinformatics analysis and luciferase assay suggested that miR-206 may target ubiquitin-specific peptidase 33 (USP33). USP33 mRNA expression has negative correlation with miR-206 expression and positive correlation with circ_0057558 expression in prostate cancer tissues. USP33 overexpression partially blocked the effects of miR-206 mimics on prostate cell proliferation. USP33 could bind and deubiquitinate c-Myc. Increased c-Myc protein by circ_0057558 overexpression was partially reversed by miR-206 mimics. The proliferation inhibition activity of MYC inhibitor 361 (MYCi361) was more prominent in primary prostate cancer cells and patient-derived xenograft (PDX) model with higher level of circ_0057558. Collectively, circ_0057558 gives an impetus to cell proliferation and cell cycle control in prostate cancer cell lines by sponging miR-206 and positively regulating the transcription of the miR-206 target gene USP33.