Department of Otolaryngology Head and Neck Surgery, Guangdong Second Provincial General Hospital, Guangzhou, China.
Department of Oncology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China.
Neoplasma. 2020 Sep;67(5):1032-1041. doi: 10.4149/neo_2020_191019N1061. Epub 2020 May 26.
Nasopharyngeal cancer (NPC) is a type of head and neck cancer with a high rate of metastasis. Circular RNAs (circRNAs) were reported to be related to the development of human cancers. This research aimed to investigate the functional mechanism of circRNA circ_0000615 in NPC. The gene expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess cell proliferation ability. Transwell assay was used to measure cell migratory and invasive abilities. Furthermore, the interaction between miR-338-3p and circ_0000615 or fibroblast growth factor 2 (FGF2) was predicted by starBase v.2.0 and then confirmed by the dual-luciferase reporter assay. Besides, the mouse xenograft experiment was carried out to explore the effect of circ_0000615 on tumor growth in vivo. We detected increased levels of circ_0000615 and FGF2, along with a decreased level of miR-338-3p in NPC tissues and cells. Circ_0000615 knockdown suppressed the proliferation, migration, invasion, and EMT of NPC cells. Interestingly, circ_0000615 interacted with miR-338-3p, and miR-338-3p targeted FGF2. Circ_0000615 inhibited miR-338-3p expression to upregulate the FGF2 level. Furthermore, both miR-338-3p depletion and FGF2 overexpression weakened the effect of circ_0000615 knockdown on NPC cell progression. Besides, circ_0000615 knockdown repressed tumor growth in vivo. In conclusion, our findings demonstrated that circ_0000615 knockdown suppressed the growth of NPC cells via modulating miR-338-3p/FGF2 axis, providing a theoretical basis for the treatment of NPC.
鼻咽癌(NPC)是一种具有高转移率的头颈部癌症。环状 RNA(circRNA)被报道与人类癌症的发展有关。本研究旨在探讨环状 RNA circ_0000615 在 NPC 中的功能机制。通过定量实时聚合酶链反应(qRT-PCR)或 Western blot 检测基因表达。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法评估细胞增殖能力。Transwell 测定用于测量细胞迁移和侵袭能力。此外,通过 starBase v.2.0 预测 miR-338-3p 与 circ_0000615 或成纤维细胞生长因子 2(FGF2)之间的相互作用,然后通过双荧光素酶报告基因测定进行验证。此外,进行了小鼠异种移植实验以探讨 circ_0000615 对体内肿瘤生长的影响。我们检测到 NPC 组织和细胞中 circ_0000615 和 FGF2 的水平升高,而 miR-338-3p 的水平降低。circ_0000615 敲低抑制 NPC 细胞的增殖、迁移、侵袭和 EMT。有趣的是,circ_0000615 与 miR-338-3p 相互作用,miR-338-3p 靶向 FGF2。circ_0000615 抑制 miR-338-3p 的表达以上调 FGF2 水平。此外,miR-338-3p 耗竭和 FGF2 过表达均削弱了 circ_0000615 敲低对 NPC 细胞进展的影响。此外,circ_0000615 敲低抑制体内肿瘤生长。总之,我们的研究结果表明,circ_0000615 敲低通过调节 miR-338-3p/FGF2 轴抑制 NPC 细胞的生长,为 NPC 的治疗提供了理论依据。