Repurposing the bitter taste receptor TAS2R14 as a pro-ferroptotic driver in thyroid cancer via the STAT3-HCG11-miR-450b-5p axis

Taste Receptor Type 2 (TAS2R) has an obvious function of sensing bitterness and transmitting neural signals. Our study aims to elucidate the upstream regulatory pathways of TAS2R14 in thyroid tumors, revealing new facets of TAS2R investigation. Bioinformatics analyses are conducted utilizing UALCAN, TargetScan, ENCORI, and GEPIA. Gene expression is assessed via microarray, qPCR, and western blot analysis. Molecular interactions are probed through dual-luciferase reporter assay, biotin-coupled pull-down, and chromatin immunoprecipitation (ChIP) assay. Ferroptosis assessment is performed using incorporated iron-centric techniques. Cellular phenotypes are determined by cell invasion, viability, apoptosis, and wound healing assays. <i>In vivo</i> studies employ a nude mouse xenograft model. We discover that TAS2R14 can inhibit thyroid cancer cell proliferation, invasion, and migration, concurrently inducing ferroptosis. The expression of TAS2R14 is governed by miR-450b-5p, which is sponged by the lncRNA HCG11 via a STAT3-dependent pathway. TAS2R14 promotes cell ferroptosis and arrests thyroid cancer progression through an upstream regulatory cascade that involves STAT3, the lncRNA HCG11, and miR-450b-5p. Our research reveals an unsuspected regulatory paradigm of the TAS2R family, shedding new light on its function and extending our understanding beyond its established role in bitter taste sensation.