Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma

Abstract

Objective. To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). Methods. First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package “MethylMix”. Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylationspecific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. Results. Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. Conclusion. These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration.