Hsa_circ_0001982 通过 miR-1287-5p/MUC19 轴在低氧环境下促进乳腺癌的进展。
Hsa_circ_0001982 promotes the progression of breast cancer through miR-1287-5p/MUC19 axis under hypoxia.
机构信息
Department of Breast Cancer, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Department of Nursing, Jiangxi Health Vocational College, Nanchang, Jiangxi, China.
出版信息
World J Surg Oncol. 2021 Jun 3;19(1):161. doi: 10.1186/s12957-021-02273-8.
BACKGROUND
Breast cancer (BC) is the most commonly malignant tumor among women worldwide. Many studies have reported that circular RNAs (circRNAs) were participated in the regulation of multiple cancers development. However, the mechanism underlying hsa_circ_0001982 in breast cancer development is still unclear.
METHODS
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001982, microRNA-1287-5p (miR-1287-5p), and mucin 19 (MUC19) in BC tissues and cells under hypoxia. Moreover, glycolysis was evaluated by glucose consumption, lactic acid production, and hexokinase II (HK2) protein levels. The protein levels of cyclin D1, proliferating cell nuclear antigen (PCNA), and HK2 were determined by western blot assay. Cell proliferation, migration, and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) and transwell assays, respectively. The relationship between miR-1287-5p and circ_0001982 or MUC19 was predicted using starbase v3.0 or Targetscan, and verified by dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. The xenograft model in nude mice was established to examine the effect of circ_0001982 in vivo.
RESULTS
The levels of circ_0001982 and MUC19 were upregulated, while miR-1287-5p was downregulated in BC tissues and cells under hypoxia. Knockdown of circ_0001982 hindered glycolysis, cell viability, migration, and invasion of BC cells under hypoxia. Mechanistic studies discovered that circ_0001982 could act as a sponge for miR-1287-5p to enhance MUC19 expression in BC cells. In addition, circ_0001982 silencing reduced xenograft tumor growth by regulating miR-1287-5p/MUC19 axis.
CONCLUSION
Circ_0001982 affected BC cells glycolysis, proliferation, migration, and invasion through miR-1287-5p/MUC19 axis under hypoxia.
背景
乳腺癌（BC）是全球女性中最常见的恶性肿瘤。许多研究报道环状 RNA（circRNA）参与了多种癌症的发展调控。然而，hsa_circ_0001982 在乳腺癌发展中的作用机制尚不清楚。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测缺氧条件下 BC 组织和细胞中 circ_0001982、微小 RNA-1287-5p（miR-1287-5p）和粘蛋白 19（MUC19）的水平。此外，通过葡萄糖消耗、乳酸生成和己糖激酶 II（HK2）蛋白水平评估糖酵解。通过 Western blot 检测细胞周期蛋白 D1、增殖细胞核抗原（PCNA）和 HK2 的蛋白水平。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）和 Transwell 测定法分别评估细胞增殖、迁移和侵袭。利用 starbase v3.0 或 Targetscan 预测 miR-1287-5p 与 circ_0001982 或 MUC19 的关系，并通过双荧光素酶报告基因检测和 RNA 结合蛋白免疫沉淀（RIP）检测进行验证。建立裸鼠异种移植模型，体内检测 circ_0001982 的作用。
结果
缺氧条件下，BC 组织和细胞中 circ_0001982 和 MUC19 水平上调，miR-1287-5p 水平下调。circ_0001982 敲低抑制了缺氧条件下 BC 细胞的糖酵解、细胞活力、迁移和侵袭。机制研究发现，circ_0001982 可作为 miR-1287-5p 的海绵，增强 BC 细胞中 MUC19 的表达。此外，通过调节 miR-1287-5p/MUC19 轴，circ_0001982 沉默抑制了异种移植肿瘤的生长。
结论
circ_0001982 通过 miR-1287-5p/MUC19 轴影响缺氧条件下 BC 细胞的糖酵解、增殖、迁移和侵袭。
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