乳腺癌(BC)是全球女性常见的癌症。新出现的证据表明环状RNAhsa-circ_0007255(circ_0007255)是BC进展中的预后介质。然而,需要确定circ_0007255的功能作用。
circ_0007255,microRNA(miR)-335-5p,使用定量实时聚合酶链反应(qRT-PCR)或蛋白质印迹测定法评估和SIXHomeobox2(SIX2)。进行放线菌素D和RNaseR处理以分析circ_0007255的稳定性。此外,海马细胞外通量,进行集落形成和transwell分析以检测耗氧率(OCR),集落形成和细胞移动,分别。miR-335-5p与circ_0007255或SIX2之间的相互作用通过双荧光素酶报告基因测定来确认。建立异种移植瘤模型,探讨circ_0007255在体内的作用。
Circ_0007255和SIX2过表达,但miR-335-5p在BC组织和细胞中减少。Circ_0007255不存在抑制耗氧量,菌落形成,细胞迁移和侵袭,并且这些效应在BC细胞中通过miR-335-5p上调被特别消除。此外,SIX2缺乏消除了miR-335-5p抑制剂对氧消耗的促进作用,菌落形成,和BC细胞中的细胞移动性。重要的是,circ_0007255在体内抑制肿瘤生长。机械上,circ_0007255是miR-335-5p的海绵,以调节BC进展中的SIX2表达。
Circ_0007255通过调节miR-335-5p/SIX2轴,在BC的进展中充当新的癌基因,并且可能是BC治疗的有希望的生物标志物。
这项研究的重要发现:circ_0007255和SIX2的水平上调,但miR-335-5p在BC组织和细胞中减少。Circ_0007255是BC发育中的癌基因,并通过miR-335-5p/SIX2轴在BC中发挥其功能。由于缺乏circ_0007255,肿瘤生长减少。
Circ_0007255通过调节miR-335-5p/SIX2轴,在BC的进展中充当新的癌基因,并且可能是BC治疗的有希望的生物标志物。
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.
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.
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.
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.
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.
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.