Circ_0079558 promotes papillary thyroid cancer progression by binding to mir-26b-5p to activate met/akt signaling

Abstract

Circular RNAs (circRNAs) are a group of non-coding RNAs featured by covalently closed circular structure. CircRNA_0079558 (circ_0079558) is derived from RAPGEF5 gene, and it has been found to be significantly up-regulated in papillary thyroid carcinoma (PTC). However, the role and working mechanism of circ_0079558 in PTC progression have never been illustrated. The levels of circ_0079558 and MET proto-oncogene, receptor tyrosine kinase (MET) were up-regulated in PTC tissues and cell lines, as evidenced by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The silencing of circ_0079558 or MET restrained cell proliferation, migration and invasion whereas triggered cell apoptosis in PTC cells, as verified by Cell Counting Kit-8 (CCK8) assay, plate colony formation assay, transwell invasion assay, wound healing assay and flow cytometry. Through using MET specific inhibitor PHA665752, we found that circ_0079558 overexpression enhanced the malignant behaviors of PTC cells through activating MET/AKT pathway. Through dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, microRNA-26b-5p (miR-26b-5p) was identified to be the intermediary molecular between circ_0079558 and MET, and circ_0079558 knockdown reduced the expression of MET partly through elevating miR-26b-5p in PTC cells. The miR-198/FGFR1 pathway was identified as another signal axis downstream of circ_0079558, and the co-overexpression of FGFR1 and MET largely rescued the proliferation ability of circ_0079558-silenced PTC cells. Through xenograft tumor model, we found that circ_0079558 silencing restrained xenograft tumor growth in vivo. In conclusion, circ_0079558 facilitated the proliferation and motility whereas inhibited the apoptosis of PTC cells largely through mediating miR-26b-5p/MET/AKT signaling.