Construction of a competing endogenous RNA network and identification of ITGA2 as a potential target in papillary thyroid carcinoma

Abstract

Background Papillary thyroid carcinoma (PTC) stands as the prevalent malignancy within the endocrine system. This study's primary aim is to probe the domain of potential biomarkers associated with PTC Methods Datasets from GEO and TCGA databases were used to analyze the differentially expressed mRNAs (DE-mRNAs), miRNA (DE-miRNAs), and methylated DNAs, which were further integrated to establish a mRNAs-miRNAs-mRNAs competing endogenous RNA (ceRNA) network by the integrative bioinformatics analyses. Additionally, pathway enrichment analysis was performed to reveal the functions of the ceRNAs by means of Metascape. qRT-PCR and western blot were used to evaluate the expression level of several genes. Methylation-specific PCR was used to assess the methylation levels of Integrin Subunit Alpha 2 (ITGA2) promoter. CCK-8 and transwell assays were used to investigate the biological function of ITGA2. Results 160 potential ceRNA pairs were identified from the intersection of mRNA-miRNA-mRNA regulatory network. Simultaneously, 970 methylated genes including 127 hypermethylated and 843 hypomethylated were recognized by overlapping the methylation datasets. Then, we retained 51 methylation-related ceRNA pairs. KEGG pathway enrichment analysis revealed that the 51 genes were primarily involved in ECM-receptor interaction and proteoglycans in cancer. Finally, we demonstrated that ITGA2 acted as an oncogene in thyroid cancer. Conclusion Our study constructed an intricate mRNA-miRNA-mRNA regulatory network as well as pinpointed numerous prospective candidates within the domain of thyroid cancer. Furthermore, our findings suggest that ITGA2 could potentially serve as a viable target in the treatment of thyroid cancer.