Knockdown of tripartite motif 59 (TRIM59) inhibits tumor growth in prostate cancer

摘要

OBJECTIVE: Members of the tripartite motif (TRIM) protein family contain a highly conserved N-terminal really interesting new gene (RING) domain that is involved in regulating transcriptional factors and tumor suppressors. In this study, the effects of TRIM59 expression on tumor growth were investigated in prostate cancer. MATERIALS AND METHODS: The expression of TRIM59 in prostate cancer tissues (n = 15) and prostate cancer cell lines was determined by quantitative reverse transcriptase-PCR (qRT-PCR), Western blotting, and immunohistochemistry. A specific shRNA targeting TRIM59 was employed to knockdown TRIM59 expression in the prostate cancer cell lines PC3 and DU145. The effects of TRIM59 knockdown on cell proliferation were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The effects on cell cycle progression were determined by flow cytometry, and a xenograft mouse model of prostate cancer was generated to determine the in vivo effects of TRIM59 knockdown. The effects on cell cycle regulators were determined by Western blotting. RESULTS: TRIM59 was highly expressed in prostate cancer tissues. Knockdown of TRIM59 significantly inhibited cell proliferation and colony formation, and cell cycle analysis showed that TRIM59-depleted cells accumulated in S-phase. TRIM59 knockdown was shown to inhibit tumorigenesis in mice. In addition, the cell cycle regulators CDC25A, CDC2, and cyclin B1 were decreased by TRIM59 shRNA-mediated knockdown. CONCLUSIONS: Our study suggests that TRIM59 promotes prostate cancer cell proliferation, possibly through its effects on cell cycle progression.