Circular RNA Profiling Reveals Exosomal circ_0006156 as a Novel Biomarker in Papillary Thyroid Cancer

Abstract

Circular RNAs (circRNAs) are a class of noncoding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, the function of circ_0006156 (circFNDC3B) was investigated in human PTC cells. First, we detected the expression of circFNDC3B in PTC tissues and PTC cell lines by RT-PCR. A luciferase reporter assay and AGO2-RNA immunoprecipitation (RIP) was used to confirm the relationship between circFNDC3B and microRNA (miR)-1178. PTC cells were stably transfected with small interfering RNA (siRNA) against circFNDC3B, and cell proliferation, migration, and invasion were detected to evaluate the effect of circFNDC3B in PTC, while tumorigenesis was assayed in nude mice. In this study, circFNDC3B was observed to be upregulated in PTC tissues and cell lines. Knockdown of circFNDC3B inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circFNDC3B/miR-1178/Toll-like receptor 4 (TLR4) axis in PTC. The dual-luciferase reporter system validated the direct interaction of circFNDC3B, miR-1178, and TLR4. Furthermore, circFNDC3B facilitates PTC progression in vivo. Importantly, we demonstrated that circFNDC3B was upregulated in serum exosomes from PTC patients. In summary, our study demonstrated that circFNDC3B modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicated that circFNDC3B may serve as a promising therapeutic target for the treatment of PTC patients.

Keywords: PTC; TLR4; ceRNAs; circFNDC3B; exosome; miR-1178.