Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of General Surgery, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, China.
Life Sci. 2021 Jan 1;264:118622. doi: 10.1016/j.lfs.2020.118622. Epub 2020 Oct 22.
In the present study, we aimed to uncover the potential functions of circular RNA (circRNA) pleckstrin and Sec7 domain containing 3 (circ_PSD3) in papillary thyroid carcinoma (PTC) development.
The abundance of circ_PSD3, PSD3 messenger RNA (mRNA), microRNA-637 (miR-637) and hemogen (HEMGN; EDAG-1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to measure cell cycle progression and cell apoptosis. Western blot assay was used to examine protein expression. The proliferation ability and motility of PTC cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays, respectively. The interaction between miR-637 and circ_PSD3 or HEMGN was tested by dual-luciferase reporter assay. Animal experiments were used to explore the role of circ_PSD3 in PTC progression in vivo.
Circ_PSD3 was aberrantly up-regulated in PTC tumor tissues compared with adjacent normal tissues. Circ_PSD3 and HEMGN promoted the cell cycle progression, proliferation and metastasis and impeded the apoptosis of PTC cells. MiR-637 was a direct target of circ_PSD3, and miR-637 directly interacted with HEMGN mRNA in PTC cells. Circ_PSD3 silencing-induced effects in PTC cells were partly attenuated by the addition of anti-miR-637 or HEMGN overexpression plasmid. Circ_PSD3/miR-637/HEMGN regulated the activity of PI3K/Akt signal pathway in PTC cells. Circ_PSD3 silencing inhibited the tumor growth in vivo.
Circ_PSD3 promoted the progression of PTC through regulating miR-637/HEMGN axis and activating PI3K/Akt signaling. Circ_PSD3/miR-637/HEMGN signaling axis might be a potential target for PTC therapy.
本研究旨在揭示环状 RNA（circRNA）pleckstrin 和 Sec7 结构域包含 3（circ_PSD3）在甲状腺乳头状癌（PTC）发展中的潜在功能。
通过实时定量聚合酶链反应（qRT-PCR）检测 circ_PSD3、PSD3 信使 RNA（mRNA）、microRNA-637（miR-637）和 hemogen（HEMGN；EDAG-1）mRNA 的丰度。采用流式细胞术检测细胞周期进程和细胞凋亡。Western blot 检测蛋白表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定和 Transwell 测定分别分析 PTC 细胞的增殖能力和迁移能力。通过双荧光素酶报告基因检测验证 miR-637 与 circ_PSD3 或 HEMGN 的相互作用。动物实验用于体内研究 circ_PSD3 在 PTC 进展中的作用。
与相邻正常组织相比，PTC 肿瘤组织中 circ_PSD3 表达异常上调。Circ_PSD3 和 HEMGN 促进 PTC 细胞的细胞周期进程、增殖和转移，抑制细胞凋亡。miR-637 是 circ_PSD3 的直接靶标，miR-637 在 PTC 细胞中与 HEMGN mRNA 直接相互作用。circ_PSD3 沉默在 PTC 细胞中引起的作用部分被添加抗 miR-637 或 HEMGN 过表达质粒所减弱。Circ_PSD3/miR-637/HEMGN 调节 PTC 细胞中 PI3K/Akt 信号通路的活性。Circ_PSD3 沉默抑制体内肿瘤生长。
Circ_PSD3 通过调节 miR-637/HEMGN 轴和激活 PI3K/Akt 信号促进 PTC 的进展。Circ_PSD3/miR-637/HEMGN 信号轴可能是 PTC 治疗的潜在靶点。
