环状 RNA 0007255 通过 miR-335-5p/SIX2 轴调控乳腺癌的进展。
Circular RNA 0007255 regulates the progression of breast cancer through miR-335-5p/SIX2 axis.
机构信息
Department of Radiology, East Hospital, Xiamen University, Fuzhou, China.
Department of Radiology, Zhengxing Hospital, Zhangzhou, China.
出版信息
Thorac Cancer. 2020 Mar;11(3):619-630. doi: 10.1111/1759-7714.13306. Epub 2020 Jan 21.
BACKGROUND
Breast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa-circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined.
METHODS
The expression of circ_0007255, microRNA (miR)-335-5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR-335-5p and circ_0007255 or SIX2 was confirmed via dual-luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo.
RESULTS
Circ_0007255 and SIX2 were overexpressed, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR-335-5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR-335-5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR-335-5p to regulate SIX2 expression in BC progression.
CONCLUSION
Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment.
KEY POINTS
Significant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR-335-5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR-335-5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence.
WHAT THIS STUDY ADDS
Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR-335-5p/SIX2 axis, and might be a promising biomarker for BC treatment.
背景
乳腺癌（BC）是全世界女性中常见的癌症。新出现的证据表明，环状 RNA hsa-circ_0007255（circ_0007255）是 BC 进展中的一种预后介质。然而，circ_0007255 的功能作用仍需确定。
方法
采用实时定量聚合酶链反应（qRT-PCR）或 Western blot 检测 circ_0007255、微小 RNA（miR）-335-5p 和六家族同源盒 2（SIX2）的表达。采用放线菌素 D 和核糖核酸酶 R 处理来分析 circ_0007255 的稳定性。此外，通过 Seahorse 细胞外通量、集落形成和 Transwell 分析分别检测氧消耗率（OCR）、集落形成和细胞迁移。通过双荧光素酶报告基因检测证实 miR-335-5p 与 circ_0007255 或 SIX2 之间的相互作用。建立异种移植肿瘤模型以探讨 circ_0007255 在体内的作用。
结果
circ_0007255 和 SIX2 表达上调，而 miR-335-5p 在 BC 组织和细胞中减少。circ_0007255 缺失抑制了 BC 细胞中的氧消耗、集落形成、细胞迁移和侵袭，并且这些作用在 BC 细胞中通过 miR-335-5p 的上调而特别被消除。此外，SIX2 缺失消除了 miR-335-5p 抑制剂对 BC 细胞中氧消耗、集落形成和细胞迁移能力的促进作用。重要的是，circ_0007255 在体内抑制了肿瘤生长。机制上，circ_0007255 是 miR-335-5p 的海绵，调节 BC 进展中的 SIX2 表达。
结论
circ_0007255 通过调节 miR-335-5p/SIX2 轴在 BC 进展中发挥新型致癌基因的作用，并且可能是 BC 治疗的有前途的生物标志物。
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