Department of Thyroid Surgery.
Department of Ultrasound Medicine, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China.
Anticancer Drugs. 2022 Oct 1;33(9):923-934. doi: 10.1097/CAD.0000000000001382. Epub 2022 Sep 14.
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.
先前的研究表明，环状 RNA（circRNAs）参与了甲状腺乳头状癌（PTC）的进展。然而，circ_0002111 在 PTC 中的机制尚不清楚。在这项研究中，通过实时定量 PCR 测量 circ_0002111、微小 RNA（miRNAs）和高迁移率族蛋白 1（HMGB1）的表达。应用免疫组织化学检测和 Western blot 测定蛋白质水平。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐和胸苷类似物 5-乙炔基-2'-脱氧尿苷测定分别评估 PTC 细胞活力和增殖。此外，通过流式细胞术、Transwell 和管形成测定分别确定细胞凋亡、侵袭和血管生成能力。此外，通过双荧光素酶报告基因测定证实了 miR-363-3p 与 circ_0002111 或 HMGB1 之间的相互作用。最后，我们建立了异种移植模型以检查 circ_0002111 在体内的功能。结果发现，circ_0002111 在 PTC 组织和细胞中表达增强。沉默 circ_0002111 明显减缓了 PTC 细胞的活力、增殖、侵袭和管形成，并加速了细胞凋亡。此外，circ_0002111 敲低抑制了体内肿瘤的生长。对于机制分析，circ_0002111 通过海绵吸附 miR-363-3p 来调节 HMGB1 的表达。此外，miR-363-3p 抑制剂恢复了 circ_0002111 敲低引起的细胞恶性表型的影响。此外，miR-363-3p 过表达通过靶向 PTC 中的 HMGB1 影响细胞功能。因此，沉默 circ_0002111 通过 miR-363-3p/HMGB1 轴限制了 PTC 的进展，这也许为 PTC 的治疗提供了新的思路。
