环状 RNA circHMCU 通过 miR-4458/PGK1 调控级联促进乳腺癌发生。
Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade.
机构信息
Department of Thyroid and Breast Surgery, Nanyang Second General Hospital, NO. 66, Jianshe East Road, Nanyang, 473000, Henan Province, China.
Department of Radiotherapy, Nanyang Second General Hospital, Nanyang, 473000, Henan Province, China.
出版信息
Hereditas. 2023 Mar 23;160(1):12. doi: 10.1186/s41065-023-00275-y.
BACKGROUND
Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.
METHODS
The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5'-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.
RESULTS
CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.
CONCLUSION
CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.
背景
环状 RNA（circRNAs）在乳腺癌（BC）中表达异常。然而，circHMCU 的生物学功能和机制仍需要进一步探讨。
方法
采用实时定量聚合酶链反应（qRT-PCR）或 Western blot 检测 circHMCU、miR-4458 和磷酸甘油酸激酶 1（PGK1）的表达水平。通过相关商业试剂盒检测葡萄糖摄取、乳酸生成和 ATP 水平。细胞计数试剂盒-8（CCK8）、5'-乙炔基-2'-脱氧尿苷（EdU）和流式细胞术分别用于检测细胞增殖和凋亡。Transwell 和划痕愈合实验用于检测细胞迁移和侵袭能力。双荧光素酶报告实验验证 circHMCU、miR-4458 和 PGK1 之间的关系。动物研究评估 circHMCU 在肿瘤生长中的作用。
结果
circHMCU 在 BC 组织和细胞系中上调，而 miR-4458 下调。在生物学实验中，circHMCU 敲低抑制细胞增殖、迁移、糖酵解，同时促进细胞凋亡。circHMCU 与 miR-4458 结合，miR-4458 靶向 PGK1。miR-4458 抑制逆转了 circHMCM 敲低对 BC 细胞恶性行为的影响。miR-4458 过表达通过上调 PGK1 抑制 BC 细胞糖酵解、增殖和转移，促进凋亡。此外，circHMCU 抑制体内肿瘤生长。
结论
circHMCU 通过调节 BC 中的 miR-4458/PGK1 轴发挥致癌作用。
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