SHCBP1 contributes to the proliferation and self-renewal of cervical cancer cells and activation of the NF-[kappa]B signaling pathway through EIF5A

Cervical cancer (CC) is the most common human papillomavirus-related disease. Continuous activation of the NF-[kappa]B signaling pathway has been observed in CC. SHC binding and spindle associated 1 (SHCBP1) contributes to tumorigenesis and activation of the NF-[kappa]B pathway in multiple cancer types, while its function in CC remains unclear. In the present study, three Gene Expression Omnibus datasets were used to identify differentially expressed genes (DEGs) in CC. Loss- and gain-of-function experiments were performed using stable SHCBP1-silenced and SHCBP1-overexpressing CC cells. To further explore the molecular mechanism of SHCBP1 in CC, small interfering RNA targeting eukaryotic translation initiation factor 5A (EIF5A) was transfected into stable SHCBP1-overexpressing CC cells. The results demonstrated that SHCBP1 was an upregulated DEG in CC tissues compared with healthy control cervical tissues. Functional experiments revealed the pro-proliferative and pro-stemness role of SHCBP1 in CC cells (CaSki and SiHa cells), in vitro. Furthermore, the NF-[kappa]B signaling pathway in CC cells was activated by SHCBP1. Increases in cell proliferation, stemness and activation of NF-[kappa]B, induced by SHCBP1 overexpression in CC cells, were reversed by EIF5A knockdown. Taken together, the results indicated that SHCBP1 serves an important role in regulation of CC cell proliferation, self-renewal and activation of NF-[kappa]B via EIF5A. The present study demonstrated a potential molecular mechanism underlying the progression of CC. Key words: SH2 domain-binding protein, eukaryotic translation initiation factor 5A, cervical cancer, nuclear factor-[kappa]B