The oncogenic role of the circ_0003997/miR-370-3p/HMGA2 axis in papillary thyroid cancer.

[BACKGROUND] Papillary thyroid cancer (PTC) is the most common endocrine malignancy, demonstrating the most rapid incidence growth among solid tumors in the past decades. Notably, aggressive variants frequently manifest metastatic potential and therapeutic resistance, substantially compromising poor prognosis. Circular RNAs (circRNAs) have been recognized as pivotal regulators in diverse biological processes across multiple cancer types. However, the molecular mechanism underlying circ_0003997 (circCLMP) in PTC remains largely unexplored.

[METHODS] The expression levels of circ_0003997, miR-370-3p, and HMGA2 were assessed using real-time quantitative polymerase chain reaction (RT-qPCR). The functions of circ_0003997 were evaluated through CCK-8 assays, wound healing assays, and Transwell assays in PTC cells. Western blotting was used to analyze the expression of key epithelial-mesenchymal transition (EMT) proteins. Tumor development in vivo was assessed using xenograft tumor models. The expression of Ki67 and HMGA2 in tumor tissues was evaluated by immunohistochemical (IHC) assay. Dual-luciferase reporter assays were performed to validate the interactions among circ_0003997, HMGA2, and miR-370-3p.

[RESULTS] Circ_0003997 demonstrated significant upregulation in PTC tissues and cells. Functional validation experiments revealed that knockdown of circ_0003997 inhibited cell proliferation, migration, invasion, and EMT, while its overexpression promoted PTC progression. Mechanistically, circ_0003997 modulated HMGA2 expression by sponging miR-370-3p. Rescue experiments demonstrated that the oncogenic effects of circ_0003997 could be reversed by miR-370-3p. In vivo data showed that the decreased expression of circ_0003997 significantly suppressed tumor growth of PTC.

[CONCLUSIONS] We identified a novel biomarker panel consisting of the circ_0003997/miR-370-3p/HMGA2 axis, offering potential diagnostic and therapeutic avenues for PTC.