Circular RNA circFOXM1 Plays a Role in Papillary Thyroid Carcinoma by Sponging miR-1179 and Regulating HMGB1 Expression

Mol Ther Nucleic Acids. 2020 Mar 6:19:741-750. doi: 10.1016/j.omtn.2019.12.014. Epub 2019 Dec 20.

Abstract

Circular RNAs (circRNAs) are a class of noncoding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, we attempted to provide a novel basis for targeted therapy for PTC from the aspect of the circRNA-microRNA (miRNA)-mRNA interaction. We investigated the expression of circRNAs in five paired PTC tissues and normal tissues by microarray analysis. The circRNA microarray assay followed by qRT-PCR was used to verify the differential expression of circFOXM1 (hsa_circ_0025033), which is located at chr12: 2966846-2983691 and derived from FOXM1. The spliced length of circFOXM1 is 3410 nt. The qRT-PCR analysis was to investigate the expression pattern of circFOXM1 in PTC tissues and cell lines. Then, the effects of circFOXM1 on tumor growth were assessed in PTC in vitro and in vivo. Furthermore, bioinformatics online programs predicted, and the luciferase reporter assay was used to validate the association of circFOXM1 and miR-1179 in PTC cells. In this study, circFOXM1 was observed to be upregulated in PTC tissues and cell lines. circFOXM1 downregulation inhibited tumor growth of PTC in vitro and in vivo. Bioinformatics analysis predicted that there is a circFOXM1/miR-1179/high-mobility group box 1 (HMGB1) axis in PTC. A dual luciferase reporter system validated the direct interaction of circFOXM1, miR-1179, and HMGB1. In summary, our study demonstrated that circFOXM1 modulates cancer progression through the miR-1179/HMGB1 pathway in PTC. Our findings indicate that circFOXM1 may serve as a promising therapeutic target for the treatment of PTC patients.

Keywords: PTC; ceRNA; circFOXM1; circRNAs; target.