Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis.

Aims: In the present study, we aimed to uncover the potential functions of circular RNA (circRNA) pleckstrin and Sec7 domain containing 3 (circ_PSD3) in papillary thyroid carcinoma (PTC) development.

Main Methods: The abundance of circ_PSD3, PSD3 messenger RNA (mRNA), microRNA-637 (miR-637) and hemogen (HEMGN; EDAG-1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to measure cell cycle progression and cell apoptosis. Western blot assay was used to examine protein expression. The proliferation ability and motility of PTC cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays, respectively. The interaction between miR-637 and circ_PSD3 or HEMGN was tested by dual-luciferase reporter assay. Animal experiments were used to explore the role of circ_PSD3 in PTC progression in vivo.

Key Findings: Circ_PSD3 was aberrantly up-regulated in PTC tumor tissues compared with adjacent normal tissues. Circ_PSD3 and HEMGN promoted the cell cycle progression, proliferation and metastasis and impeded the apoptosis of PTC cells. MiR-637 was a direct target of circ_PSD3, and miR-637 directly interacted with HEMGN mRNA in PTC cells. Circ_PSD3 silencing-induced effects in PTC cells were partly attenuated by the addition of anti-miR-637 or HEMGN overexpression plasmid. Circ_PSD3/miR-637/HEMGN regulated the activity of PI3K/Akt signal pathway in PTC cells. Circ_PSD3 silencing inhibited the tumor growth in vivo.

Significance: Circ_PSD3 promoted the progression of PTC through regulating miR-637/HEMGN axis and activating PI3K/Akt signaling. Circ_PSD3/miR-637/HEMGN signaling axis might be a potential target for PTC therapy.