Circ_0011373 promotes papillary thyroid carcinoma progression by regulating miR-1271/LRP6 axis.

Abstract

This research aimed to explore the regulatory molecular mechanism among circular RNA (circ)_0011373, microRNA (miR)-1271, and lipoprotein receptor-related protein 6 (LRP6) in papillary thyroid carcinoma (PTC). Quantitative real-time PCR (qRT-PCR) assay was adopted to measure the expression of circ_0011373, miR-1271, and LRP6 mRNA. Furthermore, cell cycle distribution, apoptosis, migration and invasion were investigated by flow cytometry and transwell assay, respectively. The target relationship between miR-1271 and circ_0011373 or LRP6 was predicted by using the Starbase website and DIANA TOOL and verified by dual-luciferase reporter and RIP assay. Protein expression levels of LRP6, p-mTOR, mTOR, p-AKT, AKT, p-PI3K, and PI3K were tested by Western blot. The function of circ_0011373 on PTC tumor growth was validated by the xenograft tumor model in vivo. Circ_0011373 and LRP6 were upregulated, while miR-1271 was downregulated in PTC tissues and cell lines. Moreover, knockdown of circ_0011373 inhibited cell cycle, migration, and invasion and promoted apoptosis. Of particular importance was the fact that circ_0011373 directly interacted with miR-1271 and miR-1271 inhibitor was able to reverse the effect of circ_0011373 knockdown on PTC cell progression. Meanwhile, LRP6 was directly targeted by miR-1271, and its expression was positively regulated by circ_0011373. We further confirmed that miR-1271 overexpression suppressed cell cycle, migration, and invasion and enhanced apoptosis by regulating LRP6. In addition, circ_0011373 knockdown restrained PTC tumor growth in vivo. Circ_0011373 might be able to regulate PTC cell cycle, migration, invasion, and apoptosis by regulating the miR-1271/LRP6 axis.