Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 91, Issue -, Pages 1167-1177Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.05.056
Keywords
Secreted phosphoprotein 1; Colorectal cancer; Metastasis; Epithelial-mesenchymal-transition; Bioinformatics
Funding
- Clinical application of CSUS ultrasound knife in colorectal surgery [15DZ1941205]
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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 epithelialmesenchymal- 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. (C) 2017 Elsevier Masson SAS. All rights reserved.
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