Semaphorin-3F functions as a tumor suppressor in colorectal cancer due to regulation by DNA methylation.

Semaphorin-3F (SEMA3F) is a member of the class III semaphorin family, and is seen as a candidate tumor suppressor gene. The aims of this study were to evaluate the effect of SEMA3F in colorectal cancer (CRC) patients, and to explore the mechanism for that SEMA3F suppresses tumor progression and metastasis. The expression levels of SEMA3F in the colorectal cancer tissues and corresponding non-tumor colorectal tissues were determined by Western blotting and real-time quantitative PCR (qRT-PCR). In addition, we evaluate the effects of SEMA3F on CRC cell migration and colony formation in vitro. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands of SEMA3F gene promoter in normal colon and colorectal cancer cell lines, colorectal cancer tissues and corresponding non-tumor colorectal tissues. We found that SEMA3F was downregulated in the protein (P < 0.01) and mRNA (P < 0.001) levels in CRC tissues as compared to matched adjacent non-tumor tissues. Moreover, MSP assay showed high levels of SEMA3F gene promoter methylation in the CpG islands in some CRC cell lines and tissue samples. Furthermore, SEMA3F expression was reactivated in CRC cell lines after treatment with 5-Aza-CdR, demethylation of SW620 cells resulted in cell colony formation and invasion inhibition. These findings suggest DNA methylation of promoter CpG island-mediated silencing of the tumor suppressor SEMA3F gene plays an important role in the carcinogenesis of CRC.