Genome-wide analyses identify circAQR, a circular RNA suppressing proliferation but promoting migration and invasion in thyroid cancer

Thyroid cancer frequently metastasizes, even in small lesions, significantly impacting prognosis. Circular RNAs (circRNAs) have emerged as critical regulators of tumor biology; however, their roles in thyroid cancer progression remain poorly understood. Using RNA sequencing data from clinical and GEO-derived samples, we identified 111,971 circRNAs, including 13,399 novel thyroid cancer-specific circRNAs. TNM stage-specific analysis revealed 43 circRNAs positively correlated with tumor size (Rho = 1) and 168 negatively correlated (Rho = -1). Gene Ontology enrichment analysis demonstrated that the target genes of thyroid cancer-specific circRNAs are enriched in cell developmental regulation pathways (NES = 1.74, p < 0.05). Network analysis further suggested that these circRNAs function as competing endogenous RNAs by interacting with tumor-associated microRNAs. Among these, circAQR was significantly associated with tumor size and lymph node metastasis. In vitro experiments revealed that circAQR inhibits proliferation while promoting migration and invasion in thyroid cancer cell lines. These findings highlight the pivotal role of TNM stage-specific circRNAs in thyroid cancer progression, with circAQR showing potential as a biomarker for early metastasis detection and a therapeutic target. The integration of circRNAs into clinical practice could improve early diagnosis and prognostic evaluation, contributing to more effective management of thyroid cancer.