Department of Otorhinolaryngology, An'kang Central Hospital, No.85, Jinzhou South Road, Hanbing District, Ankang, 725000, Shaanxi, China.
Biochem Genet. 2022 Dec;60(6):2069-2086. doi: 10.1007/s10528-022-10205-8. Epub 2022 Mar 3.
Circular RNAs function as important regulators in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). We aimed to explore the functions of circ_0028007 in NPC development. Quantitative real-time polymerase chain reaction assay was employed for the levels of circ_0028007, NUAK family kinase 1, microRNA-656-3p (miR-656-3p), and E74 like ETS transcription factor 2 (ELF2). RNase R assay was used to verify the feature of circ_0028007. Cell Counting Kit-8 assay and colony formation assay were performed to assess cell growth. Wound-healing assay and transwell assay were adopted to analyze cell migration and invasion. Tube formation assay was conducted for cell angiogenic capacity. Flow cytometry analysis was performed for cell apoptosis. Western blot assay was conducted for protein levels. Compared to normal tissues and cells, circ_0028007 level was elevated in NPC tissues and cells. Knockdown of circ_0028007 repressed NPC cell growth, migration, invasion, and angiogenesis, facilitated apoptosis in vitro and blocked tumor growth in vivo. Moreover, circ_0028007 silencing could regulate the AMP-activated protein kinase/mammalian target of rapamycin pathway in NPC cells. Circ_0028007 promoted the malignant behaviors of NPC cells via acting as miR-656-3p sponge. In addition, ELF2 was demonstrated to be the target gene of miR-656-3p. MiR-656-3p overexpression restrained NPC cell malignant phenotypes, while ELF2 elevation reversed the effects. Circ_0028007 contributed to the progression of NPC by decoying miR-656-3p and elevating ELF2. The findings might provide potential targets for NPC therapy.
环状 RNA 作为重要的调节因子，参与人类癌症的发病机制，包括鼻咽癌（NPC）。我们旨在探讨 circ_0028007 在 NPC 发展中的作用。采用实时定量聚合酶链反应检测 circ_0028007、NUAK 家族激酶 1、微小 RNA-656-3p（miR-656-3p）和 E74 样 ETS 转录因子 2（ELF2）的水平。采用核糖核酸酶 R 试验验证 circ_0028007 的特征。通过细胞计数试剂盒-8 试验和集落形成试验评估细胞生长。采用划痕愈合试验和 Transwell 试验分析细胞迁移和侵袭。管形成试验用于评估细胞的血管生成能力。采用流式细胞术分析细胞凋亡。通过 Western blot 试验检测蛋白水平。与正常组织和细胞相比，NPC 组织和细胞中 circ_0028007 水平升高。circ_0028007 敲低抑制 NPC 细胞生长、迁移、侵袭和血管生成，促进体外细胞凋亡并阻断体内肿瘤生长。此外，circ_0028007 沉默可调节 NPC 细胞中的 AMP 激活蛋白激酶/雷帕霉素靶蛋白通路。circ_0028007 通过作为 miR-656-3p 海绵促进 NPC 细胞的恶性行为。此外，ELF2 被证明是 miR-656-3p 的靶基因。miR-656-3p 过表达抑制 NPC 细胞恶性表型，而 ELF2 升高则逆转这种作用。circ_0028007 通过诱饵 miR-656-3p 和升高 ELF2 促进 NPC 的进展。这些发现可能为 NPC 治疗提供潜在的靶点。
