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环状 RNA circ_0000615 敲低通过调节 miR-338-3p/FGF2 轴抑制鼻咽癌的发展。

Circular RNA circ_0000615 knockdown suppresses the development of nasopharyngeal cancer through regulating the miR-338-3p/FGF2 axis.

机构信息

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.

出版信息

Neoplasma. 2020 Sep;67(5):1032-1041. doi: 10.4149/neo_2020_191019N1061. Epub 2020 May 26.

Abstract

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.

摘要

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。

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