Abstract
Nucleostemin (NS) is a GTP-binding protein that is predominantly expressed in embryonic and adult stem cells but not in terminally differentiated cells. NS plays an essential role in maintaining the continuous proliferation of stem cells and some types of cancer cells. However, the role of NS in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to clarify the role of NS in HCC. First, we demonstrated high expression of NS in most HCC cell lines and liver cancer tissues. NS knockdown induced a severe decline in cell viability of MHCC97H cells as detected by MTT and cell proliferation assays. Next, we used ultraviolet (UV) and serum starvation-induced apoptosis models to investigate whether NS suppression or up-regulation affects HCC cell apoptosis. After UV treatment or serum starvation, apoptosis was strongly enhanced in MHCC97H and Bel7402 cells transfected with small interfering RNA against NS, whereas NS overexpression inhibited UV- and serum-induced apoptosis of HCC cells. Furthermore, after UV irradiation, inhibition of NS increased the expression of pro-apoptosis protein caspase 3 and decreased the expression of anti-apoptosis protein Bcl-2. A caspase 3 inhibitor could obviously prevent NS knockdown-induced apoptosis. In conclusion, our study demonstrated overexpression of NS in most HCC tissues compared with their matched surrounding tissues, and silencing NS promoted UV- and serum starvation-induced apoptosis of MHCC97H and Bel7402 cells. Therefore, the NS gene might be a potential therapeutic target of HCC.
Highlights
Nucleostemin (NS), named guanine nucleotide binding protein-like 3 (GNL3), is a nucleolar protein
Western blot assays were carried out to investigate the expression of NS protein in hepatocellular carcinoma (HCC) cell lines from various sources as well as an immortalized liver cell line, L02
MTT assays indicated that HepG2, MHCC97H, SMMC7721, Bel7402 HCC cell lines had higher growth rates compared with the L02 cell line (S1 Fig)
Summary
Nucleostemin (NS), named guanine nucleotide binding protein-like 3 (GNL3), is a nucleolar protein. Mammalian NS was first cloned from neural stem cells [1]. The vertebrate NS family includes NS, GNL3, and Ngp-1, all of which contain a unique MMR1-HSR1 domain. NS Knockdown and HCC Apoptosis carcinoma; NS, nucleostemin; RT, reversetranscription; siRNA, small interfering RNA; TRF1, telomeric repeat-binding factor 1. Of five GTP-binding motifs arranged in a circularly permuted order [6]. Certain molecules regulate the partitioning of NS between the nucleolus and nucleoplasm, such as GTP and cellular senescence-inhibited gene (CSIG) [1, 7]. NS protein complex shuttling between the nucleolus and nucleoplasm might play an important role in cell proliferation and apoptosis
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