Functional and in silico evidence for the role of microRNAs 148a-5p and 199a in migration and invasion of papillary thyroid carcinoma cells

Thyroid cancer remains one of the most prevalent cancers worldwide, with lymph node metastasis (LNM) playing a critical role in determining patient prognosis and treatment. MicroRNAs (miRNAs) are essential post-transcriptional regulators of gene expression and have been implicated in cancer progression, particularly in epithelial-mesenchymal transition (EMT). This study aimed to identify miRNAs involved in the lymph node metastatic process in thyroid cancer and to evaluate their potential as therapeutic targets. RNA-seq datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used to identify dysregulated miRNAs in LNM from papillary and medullary thyroid carcinoma (PTC and MTC). The candidate miRNAs were transfected in thyroid carcinoma cell lines, TPC-1 and BCPAP, followed by quantification of target genes and analysis of cell migration and invasion assays in vitro. Three miRNAs miR-199a-5p, miR-199a-3p, and miR-148a-5p were identified as downregulated in thyroid cancer with LNM. Transfection of TPC-1 and BCPAP cells with mimetics reduced cell migration and invasion. Additionally, these miRNAs modulated the expression of EMT-related genes, particularly in BCPAP cells. Our results indicate that miR-199a-3p, miR-199a-5p, and miR-148a-5p are involved in key metastatic processes, suggesting their relevance as potential biomarkers and/or therapeutic targets for thyroid tumors. Further in vivo validation and clinical studies are required to explore their translational applications.