Long Non-Coding RNA LINC01614 Promotes Aggressive Phenotypes and Ferroptosis Resistance in Papillary Thyroid Cancer Through a Putative miR-4521/IGF2/PI3K-AKT Signaling Axis

Background/Objectives: Papillary thyroid cancer (PTC) is the most common endocrine malignancy and is generally associated with favorable clinical outcomes. However, a subset of tumors develops aggressive phenotypes characterized by increased proliferation, migration, therapeutic resistance, and disease progression. Long non-coding RNAs (lncRNAs) have emerged as important regulators of tumor biology, yet the role of Long Intergenic Non-Protein Coding RNA 1614 (LINC01614) in PTC remains poorly understood. This study investigated the functional role of LINC01614 in PTC and its potential involvement in ferroptosis-associated molecular pathways.

Methods

RNA sequencing data from a repository of 44 paired PTC and adjacent normal thyroid tissue samples were analyzed to identify differentially expressed lncRNAs. LINC01614 expression was evaluated in thyroid cell lines, and CRISPR interference (CRISPRi) was used to generate stable LINC01614 knockdown K1 cell lines. Cellular proliferation, migration, clonogenicity, intracellular iron accumulation, lipid peroxidation, cytokine secretion, and ferroptosis-associated gene expression were assessed using qRT-PCR, RNA sequencing, Western blotting, cytokine array analysis, iron quantification assays, and BODIPY C11 lipid peroxidation imaging.