Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo

摘要

Background The nucleosome binding protein 1 (HMGN5/NSBP1) is a member of the HMGN protein family and is highly expressed in several kinds of cancer. Nevertheless, the role of NSBP1 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to confirm the oncogenic role of NSBP1 in ccRCC using in vitro and in vivo models and explore the mechanism by which NSBP1 contributes to ccRCC tumorigenesis. Methods NSBP1 expression was detected in renal tissues from 152 ccRCC patients by immunohistochemistry, and examined in ccRCC cell lines by RT-PCR and Western blot analysis. ccRCC cells were transfected by NSBP1 RNAi and cell viability, apoptosis and invasion were detected by cell vitality test, flow cytometry and transwell assay in vitro. Xenograft in nude mice was also employed to examine the tumorigenesis of ccRCC cells depleted of NSBP1. Results Immunohistostaining showed strong immunoreactivity of NSBP1 in all ccRCC tissues and NSBP1 expression level was associated with tumor grade (p = 0.04). NSBP1 expression at mRNA and protein levels was high in ccRCC cell lines. Knockdown of NSBP1 induced cell cycle arrest and apoptosis, and inhibited invasion in 786-O cells. Western blot analysis demonstrated increased expression of Bax and decreased expression of Bcl-2, CyclinB1, VEGF, VEGFR-2, MMP-2, MMP-9, c-fos and c-jun in 786-O cells depleted of NSBP1. In vivo study further showed that knockdown of NSBP1 affected the tumorigenesis of ccRCC cells in nude mice. Conclusions NSBP1 plays oncogenic role in ccRCCs by promoting cell proliferation and invasion, and could be exploited as a target for ccRCC treatment.