Circ_0027446 induces CLDN1 expression to promote papillary thyroid cancer cell malignancy by binding to miR-129-5p.

Background: Previous data have shown that circular RNA (circRNA) is a key regulator in papillary thyroid cancer (PTC). However, the role and the detailed mechanism of circ_0027446 in PTC progression have not been reported.

Methods: Circ_0027446, miR-129-5p, claudin 1 (CLDN1), C-myc and MMP2 expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot or immunohistochemistry (IHC) assay. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Cell proliferation was investigated by 5-Ethynyl-2'-deoxyuridine (EdU) assay and cell colony formation assay. Cell apoptosis, invasion and migration were assessed by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Dual-luciferase reporter assay was conducted to identify the associations among circ_0027446, miR-129-5p and CLDN1. The effect of circ_0027446 on PTC cell malignancy in vivo was revealed by a xenograft mouse model assay.

Results: Circ_0027446 and CLDN1 expression were significantly upregulated, while miR-129-5p expression was downregulated in PTC tissues and cells. High circ_0027446 expression was closely associated with the poor prognosis of PTC patients. Circ_0027446 depletion inhibited PTC cell proliferation, migration and invasion but increased cell apoptosis. In addition, circ_0027446 acted as a miR-129-5p sponge, and miR-129-5p bound to CLDN1. Moreover, miR-129-5p inhibitors attenuated circ_0027446 depletion-induced effects in PTC cells. CLDN1 also participated in the regulation of miR-129-5p in PTC cell tumor properties. Importantly, circ_0027446 mediated CLDN1 expression by interacting with miR-129-5p. In vivo data showed that the decreased expression of circ_0027446 led to delayed tumor formation.

Conclusion: Circ_0027446 contributed to PTC cell tumor properties by regulating the miR-129-5p/CLDN1 pathway, showing circ_0027446 might be a therapeutic target in PTC.