Hypermethylation of MIR129-2 Regulates SOX4 Transcription and Associates with Metastasis in Patients with Colorectal Cancer.

Background: MicroRNA-129-2 (miR-129-2), targeting SOX4, has been shown to be involved in the pathogenesis of different cancers. Here in this study, we examined the methylation levels of the promoter region of MIR19-2 gene as well as transcription of miR-129-2 and mRNA expression of SOX4 in the tumoral tissues from colorectal cancer (CRC) patients and compared those in the normal marginal tissues.

Methods: Fifty CRC patients with Iranian Azari ethnicity were recruited. Genomic DNAs were extracted from the tumoral and normal tissues and the methylation level of the promoter regions of the MIR129-2 gene was determined using methylation-specific PCR (MSP) by evaluating 100 CG sites. The RNA content of the samples was isolated and the transcript levels of miR-129-2 and SOX4 were measured using quantitative real-time PCR.

Results: Methylation level of the MIR192-2 promoter was significantly higher in the tumoral tissues compared to that in the normal marginal tissues (84% vs. 28%; P = 0.0041). The expression level of miR-192-2 was significantly downregulated (fold change = 0.34, P = 0.028) but SOX4 mRNA expression was upregulated (fold change = 2.7, P = 0.019) in the tumoral tissues compared to that in the normal marginal tissues. There was a significant correlation between the methylation level of the MIR192-2 promoter and the expression levels of miR-192-2 and SOX4 in the tumoral tissues. Associations were observed between the methylation of the MIR192-2 promoter and lymph node and liver metastasis.

Conclusions: It seems that MIR192-2 promoter hypermethylation might regulate the expression of SOX4 and therefore modulate metastasis in CRC.