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.

Circular RNAs (circRNAs) are a class of non-coding 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 novel basis for targeted therapy for PTC from the aspect of circRNA-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 hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. The qRT-PCR analysis was to investigate the expression pattern of circRASSF2 in PTC tissues and cell lines. Then the effects of circRASSF2 on cell proliferation and apoptosis were assessed in PTC in vitro. Furthermore, bioinformatics online programs predicted and luciferase reporter assays were used to validate the association of circRASSF2 and miR-1178 in PTC cells. In this study, circRASSF2 was observed to be upregulated in PTC tissues and cell lines. Knockdown of cir-cRASSF2 inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circRASSF2/miR-1178/TLR4 axis in PTC. A dualluciferase reporter system validated the direct interaction of circRASSF2, miR-1178, and TLR4. Furthermore, circRASSF2 facilitates PTC progression in vivo. Importantly, we demonstrated that circRASSF2 was upregulated in serum exosomes from PTC patients. In summary, our study demonstrates that circRASSF2 modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicate that circRASSF2 may serve as a promising therapeutic target for the treatment of PTC patients.

Papillary thyroid cancer (PTC) is a common malignancy and has a good prognosis after appropriate treatment. PTC cells spread mainly by lymph node metastasis (LNM), but the mechanism is not well understood. Expression of vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 2 (MMP-2) protein was studied immunohistochemically from the archived specimens of 65 PTC patients who initially presented without LNM. In this retrospective study, the frequency of expression differed significantly between thyroid cancer tissue and adjacent normal follicular epithelium (VEGF-C 78.5% and 20.0%, respectively; MMP-2 81.5% and 36.7%, respectively). LNM developed in 35 of the patients during 5 - 15 years of follow-up, by the end of which the frequencies of expression of VEGF-C and MMP-2 protein expression were 91.4% and 94.3%, respectively. Both VEGF-C and MMP-2 protein expression were significantly more frequent in PTC with LNM than without LNM. VEGF-C and MMP-2 protein expression levels were significantly correlated with LNM and it is, therefore, feasible that VEGF-C and MMP-2 may be useful as tumour markers of PTC with cervical LNM.