Circ_0002111 modulates the growth process of papillary thyroid carcinoma cells by targeting the miR-363-3p/HMGB1 axis

Abstract

Previous studies have suggested that circular RNAs (circRNAs) are engaged in the progression of papillary thyroid carcinoma (PTC). However, the mechanism of circ_0002111 in PTC is still unclear. In this study, quantitative real-time PCR was carried out to measure the expressions of circ_0002111, microRNAs (miRNAs) and high-mobility group box 1 (HMGB1). Immunohistochemistry assay and western blot were applied for the determination of protein levels. The assays of 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide and thymidine analog 5-ethynyl-2’-deoxyuridine were deployed to assess PTC cell viability and proliferation, respectively. Besides, the capacities of cell apoptosis, invasion and angiogenesis were determined by flow cytometry, transwell and tube formation assays, respectively. Moreover, the interaction between miR-363-3p and circ_0002111 or HMGB1 was confirmed using a dual-luciferase reporter assay. Lastly, we established a xenograft model for the examination of the function of circ_0002111 in vivo. It was found that the expression of circ_0002111 was enhanced in PTC tissues and cells. Silencing circ_0002111 apparently retarded the viability, proliferation, invasion and tube formation, as well as expedited the apoptosis of PTC cells. Besides, circ_0002111 knockdown impeded the growth of the tumor in vivo. For mechanism analysis, circ_0002111 adjusted the expression of HMGB1 by sponge adsorption of miR-363-3p. Moreover, miR-363-3p inhibitor regained the influence of cellular malignant phenotype caused by circ_0002111 knockdown. Additionally, miR-363-3p overexpression impacted the cell functions by targeting HMGB1 in PTC. Thus, silencing circ_0002111 constrained the progression of PTC by the miR-363-3p/HMGB1 axis, which perhaps provided a novel idea of the therapeutic in PTC.

Emerging roles of circular RNAs in regulating the hallmarks of thyroid cancer

“…For example, hsa_circ_0001821 (circPVT1) enhances TC progression by targeting miR-195, subsequently increasing its expression [ 53 ]. Furthermore, hsa _circ_0011058 [ 54 ] and hsa_circ_0082003 [ 55 ] (circ0002111) indirectly promote the translation of angiogenic proteins (VEGFA and FGF) by upregulating YAP1 and HMGB1 in thyroid cancers, respectively, thereby promoting angiogenesis in TCs.…”