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Circular RNAs (circRNAs) are a group of regulators that affect the aggressive behaviors of several types of cancer. Hsa_circ_0001666 (also referred to as hsa_circ_000742) is a newly discovered circRNA that is upregulated in human papillary thyroid carcinoma (PTC) based on microarray analysis. However, the role of hsa_circ_0001666 in PTC progression remains unknown. Thus, the aim of the present study was to determine the potential function and underlying mechanism of hsa_circ_0001666 in PTC. The results demonstrated that hsa_circ_0001666 was upregulated in both PTC clinical samples and cell lines. Its expression was associated with lymph node metastasis of patients with PTC. Knocking down hsa_circ_0001666 expression inhibited cell proliferation, as evidenced by decreased cell viability, arrest of cell cycle progression at the G 1 phase and an increase in cell cycle‑associated proteins. Apoptosis rates and expression levels of pro‑apoptotic proteins were also increased by silencing hsa_circ_0001666. In xenograft experiments, the oncogenic effect of hsa_circ_0001666 on tumor growth was verified. Additionally, luciferase reporter assays showed that hsa_circ_0001666 and ETS variant transcription factor 4 (ETV4) shared common binding sites with three microRNAs [(miRNA/miR)‑330‑5p, miR‑193a‑5p and miR‑326]. Knockdown of these miRNAs separately reversed the inhibitory effect of hsa_circ_0001666 small interfering RNAs on PTC tumor aggressiveness, and ETV4 overexpression also induced a similar effect to that of miRNA inhibitors. Thus, hsa_circ_0001666 may function as an oncogene, promoting PTC tumorigenesis via the miR‑330‑5p/miR‑193a‑5p/miR‑326/ETV4 pathway. This provides a basis for identifying potential novel therapeutic targets for PTC.

oncology reports

Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4