Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer

Abstract

Object. Thyroid cancer (TC) is a rare type of cancer which occurs as a result of environmental and genetic factors. Although different types of genetic and epigenetic changes are associated with TC, the molecular mechanism still remains unclear. SRY-box transcription factor 15 (SOX15) is an important transcription factor, and its expression is altered in many cancer types by epigenetic modifications. Recently, miR-147b overexpression has been associated with SOX15 silencing in TC. Methods. In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. Results. We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. Conclusions. Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.