circRASSF2 Acts as ceRNA and Promotes Papillary Thyroid Carcinoma Progression through miR-1178/TLR4 Signaling Pathway

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 circRASSF2 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 dual-luciferase 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.