miR-4260 serves as a prognostic biomarker and suppresses thyroid cancer progression

MicroRNAs (miRNAs) play critical roles in tumorigenesis and malignant transformation. Studies indicate aberrant expressionof miR-4260 in various cancers. However, its specific function and underlying molecular mechanisms in thyroid cancer (TC) remainpoorly understood.

Paired tumor and adjacent non-tumor tissues were collected from a cohort of 120 TC patients undergoing surgicalresection. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) quantified miR-4260 expression in clinical specimensand cell lines. The prognostic value of miR-4260 expression was evaluated using Kaplan-Meier survival analysis and multivariate Coxproportional hazards regression. The functional impact of miR-4260 on TC cell proliferation, migration, and invasion was assessed usingcell transfection, cell counting kit 8 (CCK-8) assays, and Transwell migration/invasion assays. The regulatory interaction between miR-4260and its potential target gene was validated by dual-luciferase reporter assay.

RT-qPCR analysis revealed significantly elevated miR-4260 expression in TC tissues compared to matched non-tumor tissues. High miR-4260 expression correlated significantly with larger tumor size (p = 0.035), deeper invasion depth (p = 0.038), advanced tumor-node-metastasis (TNM) stage (p = 0.022), and lymph node metastasis (LNM) (p = 0.025) compared to low expression. MultivariateCox analysis identified high miR-4260 expression as an independent predictor of poor prognosis [hazard ratio (HR) = 3.398, 95% confidenceinterval (CI): 1.559-7.406, p = 0.002]. Functional experiments demonstrated that inhibiting miR-4260 expression significantly attenuatedthe proliferative and invasive capacities of TC cells. Dual-luciferase assays validated ANK2 as a direct miR-4260 target. RT-qPCR quantification revealed significantly antagonistic expression patterns between ANK2 and miR-4260 in thyroid carcinoma specimens. Rescueexperiments further revealed that miR-4260 modulates the malignant phenotype of TC cells by negatively regulating ANK2, indicating their cooperative involvement in TC progression.

miR-4260 is critically implicated in TC advancement and unfavorable patient outcomes, establishing its bifunctional value as a clinically significant prognostic indicator and viable therapeutic candidate.