Upregulation of SOX18 in colorectal cancer cells promotes proliferation and correlates with colorectal cancer risk

Onco Targets Ther. 2018 Nov 29:11:8481-8490. doi: 10.2147/OTT.S178916. eCollection 2018.

Abstract

Background: Since colorectal cancer (CRC) is one of the most common malignant tumors worldwide, we aimed to identify the role of sex determining region Y (SRY)-box 18 (SOX18) in CRC.

Methods: RT-PCR and immunohistochemistry were employed to detect the expression of SOX18 in CRC samples. We then identified the effect of SOX18 on cell proliferation, cell cycle, and apoptosis by cell counting kit-8 (CCK-8), flow cytometry, and annexin V/PI staining, respectively. The effect of silencing SOX18 expression in CRC development was evaluated by using a xenograft mouse model.

Results: First, we found that SOX18 was overexpressed in CRC tissues and cell lines and that SOX18 levels in CRC tissues were positively associated with advanced clinical stages, vascular invasion, and lymph node metastasis. Furthermore, patients with higher expression of SOX18 had a lower survival rate. Overexpression of SOX18 significantly promoted cell proliferation, promoted S cell cycle progression, and inhibited cell apoptosis. Conversely, downregulation of SOX18 clearly weakened cell proliferation, induced G0/G1 cell cycle phase arrest, and gave rise to cell apoptosis. The results showed that shSOX18 significantly inhibited tumor growth and weight. Ki67 expression was also decreased by SOX18 silencing treatment.

Conclusion: Our study indicates that SOX18 may have a carcinogenic effect on CRC, which might provide novel insights into CRC prevention and treatment.

Keywords: CRC; biomarker; cell apoptosis; cell cycle; prognosis; sex determining region Y.