Abstract: Objective To investigate the molecular mechanism of Skp2/p27 axis involved in the occurrence and development of colorectal cancer(CRC) and to study its effect on the proliferation,migration and invasion of CRC cell line LS513 and tumorigenicity of nude mice.
Methods The expression of Skp2 and p27 in CRC tissues,paracancerous tissues,human normal colon epithelial cells CCD841CoN,different CRC cell lines LS513,SW480,HT29 and SW620 were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).LS513 cells with a growth density of 50%-60% were transfected with siRNA NC or siRNA Skp2,respectively,and divided into siRNA NC group and siRNA Skp2 group respectively,in addition,LS513 cells without transfection(LS513 group) were taken.After 24 hours of transfection or culture,the cell proliferation was detected by CCK-8 method;Transwell chamber method was used to detect cell migration and invasion;the tumorigenicity of the cells in vivo was detected by nude mice tumorigenicity test;the protein expression levels of Skp2,p27,p21,p57 and CKS1 were detected by Western Blot.
Results Skp2 mRNA and protein expression levels in CRC tissues and LS513,SW480,HT29 and SW620 cancer cells were significantly higher than those in adjacent tissues and CCD841CoN cells,the expression levels of p27 mRNA and protein were significantly lower(P<0.05),Compared with those in LS513 group and siRNA NC group,the protein expression levels of Skp2 and CKS1,cell proliferation,migration,invasion and tumorigenicity in vivo were significantly lower in siRNA Skp2 group(P<0.05),and the protein expression levels of p27,p21 and p57 were significantly higher(P<0.05).
Conclusion Skp2/p27 axis is involved in the occurrence and development of CRC.Interference with Skp2 can increase the expression of tumor suppressor proteins such as p27 in CRC cells,decrease the expression of CKS1 protein,and inhibit the growth,migration and invasion of CRC cells.

Key words: S-phase kinase-associated protein 2/p27 axis, colorectal cancer, RNA interference, cell growth, migration and invasion