Circ-MAP4K3 promotes papillary thyroid cancer progression by sponging miR-758-3p to enhance RRM2 expression.

Abstract

Papillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. PTC metastasizes more frequently in children and teenagers, although survival of these patients is usually considered excellent. Still, research on regulatory mechanisms has significant clinical implications. Circular RNAs (circRNAs) participate in PTC regulation. The present study analyzed the role of circ-MAP4K3 in PTC. High-throughput sequencing was used to determine circRNA expression differences between PTC and paracarcinoma tissues. The expression of circ-MAP4K3 was evaluated using RT-qPCR and FISH. TPC-1 and B-CPAP cell proliferation was analyzed utilizing CCK-8 and EdU, while cell migration was assessed based on Transwell and wound healing assays. The targeting relationship among circ-MAP4K3, miR-758-3p, and RRM2 was elucidated via dual-luciferase reporter assay. A xenograft mouse model was employed to determine the effect of circ-MAP4K3 on tumor formation in vivo. The expression of circ-MAP4K3 was increased in PTC tissues and cell lines compared to the levels in the control groups. Circ-MAP4K3 silencing inhibited PTC cell proliferation and migration and tumor growth both in vivo and in vitro. Bioinformatics analysis confirmed that both miR-758-3p and RRM2 were downstream targets of circ-MAP4K3. Inhibition of miR-758-3p or overexpression of RRM2 rescued the proliferation and migration abilities after circ-MAP4K3 downregulation. RRM2 overexpression also rescued the proliferation and migration abilities after miR-758-3p overexpression. Circ-MAP4K3 promotes PTC progression via the miR-758-3p/RRM2 signaling pathway.