Identification of ITGA2 as a methylation-regulated oncogene through a CeRNA network in papillary thyroid carcinoma.

[OBJECTIVE] Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. This study aimed to construct a competing endogenous RNA (ceRNA) network to identify potential molecular targets and validate their biological functions.

[METHODS] Gene expression profiles from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were integrated to construct a miRNA-mediated mRNA-mRNA network within a ceRNA framework. Pathway enrichment analysis was applied to identify candidate genes. Differential expression in clinical specimens was validated by Western blot and qRT-PCR. Functional assays were performed after target gene silencing in PTC cell lines. Methylation specific PCR (MSP) was used to assess the relationship between promoter methylation and gene expression.

[RESULTS] A total of 160 potential ceRNA pairs were identified, of which 51 were associated with methylation status. Functional enrichment analysis further narrowed the candidates to eight tumorigenesis-related genes. Among these, integrin alpha 2 (ITGA2) was significantly overexpressed in PTC tissues. ITGA2 knockdown in PTC cells markedly suppressed proliferation, invasion, and metastatic capacity. MSP analysis demonstrated reduced promoter methylation of ITGA2 in PTC cells relative to controls, indicating that its upregulation is linked to promoter hypomethylation.

[CONCLUSIONS] This study established a ceRNA regulatory network in PTC and identified ITGA2 as a potential therapeutic target. Its dysregulated expression is closely associated with epigenetic alterations, offering new insights into the molecular mechanisms of PTC progression.