SPP1, analyzed by bioinformatics methods, promotes the metastasis in colorectal cancer by activating EMT pathway.

OBJECTIVE

Tumor metastasis is still a great challenge for the prognosis of colorectal cancer (CRC). Although secreted phosphoprotein 1 (SPP1) over-expression is confirmed to associate with invasion, metastasis of CRC, the underlying mechanism by which modulates the CRC metastasis is still not fully explained.

METHOD

GDS4382 was obtained from GEO database and differentially expressed genes (DEGs) were analyzed by bioinformatics methods 55 paired samples of CRC and adjacent non-cancerous tissues were collected to detect the expression of SPP1 by q-PCR and western blot. Functional analysis of siRNA-SPP1, including proliferation, apoptosis, colony formation, cell cycle, migration, was investigated in CRC cell lines and tumor xenografts were conducted in nude mice. Protein expression of E-cadherin and vimentin was detected by western blot.

RESULTS

1887 DEGs were analyzed and selected from GDS4382, of which, SPP1 and epithelial-mesenchymal-transition (EMT) showed a close association by bioinformatics analysis. The mRNA and protein expression of SPP1 were significantly higher in CRC tissues than that in adjacent non-cancerous tissues (P<0.05). Overexpression of SPP1 closely associated with tumor invasion, metastasis and low survival in CRC. Moreover, siRNA-SPP1 repressed proliferation, cell cycle, colony formation, migration and tumor growth in vivo and promoted cell apoptosis in CRC cell lines. In addition, Protein expression of E-cadherin was obviously up-regulated and Vimentin was down-regulated in CRC cells after siRNA-SPP1 (P<0.05).

CONCLUSION

SPP1 expression was significantly up-regulated in CRC. And SPP1 promoted the metastasis of CRC by activating EMT, which could be a potentially therapeutic target for patients with CRC.