Interferon Regulatory Factor 2 (IRF2) Inhibits the Invasion and Migration of Renal Clear Cell Carcinoma Cells by Downregulation of Spindle Pole Body Component 24 (SPC24)

Abstract

It has been reported that the increased expression of SPC24 (spindle pole body component 24) was involved in the initiation and development of various cancers. However, the role of SPC24 in ccRCC (clear cell renal cell carcinoma) remains largely unknown. In the present study, the changes and correlation of SPC24 and IRF2 (interferon regulatory factor 2) with ccRCC were evaluated by using GEPIA, TCGA and GTEx database. Then the involvement of SPC24 and IRF2 in invasion and migration was investigated in CaKi-1 cells, a human renal adenocarcinoma cell line. The bioinformatics assay revealed that the expression of SPC24 and IRF2 in kidney tissue of patients with renal clear cell cancer was significantly increased, and the expression of SPC24 and IRF2 in kidney tissue was positively and negatively related to cancer phase and survival rate in patients with ccRCC respectively. Notably, in vitro experimental study demonstrated that SPC25 promoted the invasion and migration of CaKi-1 cells, a human renal adenocarcinoma cell line. Furthermore, IRF2 shows potential binding site with SPC24 promoter, IRF2 overexpression significantly decreased SPC24 mRNA level, whereas inhibition of IRF2 with specific small hairpin RNA (shRNA) significantly increased SPC24 mRNA level. Functionally, inhibition of SPC24 with specific shRNA reversed the stimulatory effect of IRF2 shRNA on the invasion and migration of cells, whereas SPC24 over-expression reversed the inhibitory effect of IRF2 overexpression on the invasion and migration of cells. Finally, ChIP (chromatin immunoprecipitation) assay shows that IRF2 could directly bind with SPC24 promoter. In conclusion, these results demonstrated that IRF2/SPC24 signaling pathway contributes to the increased invasion and migration in ccRCC.