Downregulation of tNASP inhibits proliferation through regulating cell cycle-related proteins and inactive ERK/MAPK signal pathway in renal cell carcinoma cells

Abstract

Nuclear auto-antigenic sperm protein (NASP), initially described as a highly auto-immunogenic testis and sperm-specific protein, is a histone chaperone that is proved to present in all dividing cells. NASP has two splice variants: testicular NASP (tNASP) and somatic form of NASP (sNASP). Only cancer, germ, transformed, and embryonic cells have a high level of expression of the tNASP. Up to now, little has been known about tNASP in renal cell carcinoma (RCC). In the present study, the molecular mechanism of tNASP in RCC was explored. The expression level of tNASP in 16 paired human RCC specimens was determined. Downregulation of tNASP by small interfering RNA (siRNA) was transfected in RCC cell lines. The effect of downregulation of tNASP by siRNA on cell colony formation and proliferation was examined by colony formation assay and CCK-8 assay, cell cycle was analyzed by flow cytometry, and the expression of cyclin D1 and P21 were detected by Western blotting. ERK/MAPK signaling was also analyzed. tNASP has a relative high expression level in human RCC tissues. Via upregulation of P21 and downregulation of cyclinD1, silence of tNASP can inhibit cell proliferation, which induces cell cycle arrest. Furthermore, ERK signaling pathway is confirmed to mediate the regulation of cell cycle-related proteins caused by silence of tNASP. Our research demonstrates that knockdown of tNASP effectively inhibits the proliferation and causes G1 phase arrest through ERK/MAPK signal pathway.

microRNA-29c inhibits cell proliferation by targeting NASP in human gastric cancer

“…Both types of NASP specifically bind to histone H1, H3 and H4 and affect chromatin assembly, lead to the association with DNA replication, cell proliferation and cell cycle progression [ 18 ]. Previous studies have investigated the role of NASP in renal cell carcinoma [ 19 ]. Fang et al showed that tNASP has a relative high level in human renal cell carcinoma and tNASP knockdown effectively suppresses cell proliferation and induces G1 phase arrest through ERK/MAPK signaling pathway.…”

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

“…This data suggests that the ERK1/2 signaling pathway plays a vital role in renal carcinoma proliferation, with very few reports expressing an opposite opinion. Fang et al suggested that the ERK1/2 signaling pathway mediates the regulation of cell cycle-related proteins, effectively inhibits cell proliferation, and also causes G1 phase arrest in RCC cell lines [123]. Protein kinase C epsilon (PKCε) plays as an important mediator in cancer stem cell pathogenesis of renal cell cancer by regulating the phosphorylation of ERK1/2 in RCC 769P side population cell line [124].…”

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

“…Additionally, the null mutation of NASP is embryonically lethal in mice. Furthermore, downregulated NASP inhibits cell proliferation through regulating cell cycle-related proteins in renal cell carcinoma cells 7. To analyze the crucial role of NASP in tumor progression, we tried to detect the relationship between NASP and melanoma progression, which remains unknown.…”