ASIC1 Emerges as an ATC-Associated Candidate from an Integrative Dual miRNA-mRNA Analysis

Background/Objectives: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy in which coordinated loss of tumor-suppressive miRNAs may contribute to reciprocal upregulation of shared target genes. We aimed to identify common miRNA targets associated with ATC and to prioritize candidates showing reproducible expression across independent datasets. Methods: We analyzed the matched miRNA and mRNA expression data from GSE185719, focusing on hsa-miR-125b-5p and hsa-miR-181b-5p because both were consistently reduced in ATC compared with non-malignant thyroid tissue, PTC, and FTC. Candidate targets predicted by miRWalk and supported by TargetScan and miRDB were filtered for reciprocal mRNA upregulation in ATC, then evaluated in the independent GSE33630 cohort, followed by functional enrichment and exploratory ROC analyses. Results: Both hsa-miR-125b-5p and hsa-miR-181b-5p were consistently reduced in ATC. Their predicted target sets overlapped at 55 genes, of which 13 were upregulated in ATC and seven remained consistently increased across all comparisons. ASIC1 was one of the strongest candidates, was independently elevated in GSE33630, and showed exploratory discrimination of ATC from normal thyroid and PTC (AUC 0.903 and 0.848, respectively). Both miRNAs were predicted to target ASIC1, although these interactions remain unvalidated. Conclusions: Given the proton-sensing function of ASIC1 and the importance of extracellular acidosis in aggressive tumors, these findings provide a focused hypothesis linking post-transcriptional deregulation with acid-sensing biology in ATC. Direct miRNA–ASIC1 regulation and its functional consequences require experimental validation.