Upregulation of nucleostemin in colorectal cancer and its effects on cell malignancy

Abstract

Objective: Nucleostemin (NS) is a new protein localized in the nucleolus of most stem cells and tumor cells, which regulates their self-renewal and cell cycle progression. The aim of this study was to investigate the expression of NS in colorectal cancer (CRC) and the effects of NS knockdown in the Sw620 cell line to provide basis for clinical target therapy. Methods: NS expression in 372 patients with CRC and 367 normal participants was assessed using immunohistochemistry. The expression level of NS gene was evaluated by polymerase chain reaction. Then, the relationship among NS expression, clinicopathological features, and prognosis was analyzed. Silencing of NS expression was achieved by using NS-specific small-interfering RNAs. The viability and growth rate of Sw620 cells were determined by proliferation and invasion assays. Cell cycle distribution of the cells was analyzed by flow cytometry. Results: High NS expression was positively related with node metastasis, distant metastasis, and TNM stage. In Kaplan–Meier survival analysis, patients with low NS expression always had significantly longer survival time than those with high expression. Moreover, our results showed that knockdown of NS expression inhibited proliferation and viability of Sw620 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G1 cell cycle arrest at short times of transfection (24hours), followed with apoptosis at longer times (48hours and 72hours), suggesting that post-G1 arrest apoptosis occurred in Sw620 cells. Conclusion: Overall, these results point to the essential role of NS in Sw620 cells; thus, this gene might be considered a promising target for treatment of CRC.