ABSTRACT
【Objective】 To investigate the role of RRM2 in prostate cancer and the mechanism. 【Methods】 The data of prostate cancer expression profile were downloaded from The Cancer Genome Atlas (TCGA). The correlation between RRM2 expression and clinicopathological features and prognosis of prostate cancer was analyzed. The protein expressions of RRM2 in 55 cases of prostate cancer and 38 benign tissues were determined with immunohistochemistry (IHC). The effects of RRM2 on the biological process of prostate cancer were assessed with bioinformatic analysis. The biological process of RRM2 affecting the progression of prostate cancer was verified with Western blot and flow cytometry. 【Results】 RRM2 was highly expressed in prostate cancer, and the expression was positively correlated with the clinical stage, pathological grade and metastasis of prostate cancer (P<0.05). Higher RRM2 expression predicted poorer survival. RRM2 co-expression positively correlated genes were involved in cell cycle pathways, pyrimidine nucleotide metabolism, and biological processes such as RNA transport. Cell cycle pathways were significantly enriched. RRM2 was highly correlated with CDK1 and PCNA molecules. RRM2 knockdown reduced the protein expressions of CDK1 and PCNA in DU145 and LNCap cell lines, which were arrested in the G2/M phase. 【Conclusion】 RRM2 promotes tumor progression by interfering with G2/M cycle of prostate cancer cells.
ABSTRACT
Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged. Chk1 is specifically phosphorylated by ATR (ATM-RAD3-related gene). Western blot analysis showed that phospho-ATR was activated by DADS. Taken together, these data suggest that cell cycle G2/M arrest, which was associated with accumulation of the phosphorylated forms of Chk1, but not of Chk2, was involved in the growth inhibition induced by DADS in the human gastric cancer cell line BGC823. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/Cdc25C/cyclin B1, and is independent of Chk2.