Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored. 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. 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. CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.

中文翻译：

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环状 RNA circHMCU 通过 miR-4458/PGK1 调控级联促进乳腺肿瘤发生

环状 RNA (circRNA) 在乳腺癌 (BC) 中异常表达。然而，circHMCU的生物学功能和机制仍需进一步探索。通过定量实时聚合酶链反应（qRT-PCR）或蛋白质印迹测量circHMCU、miR-4458和磷酸甘油酸激酶1（PGK1）的表达水平。通过相关的商业试剂盒测定葡萄糖摄取、乳酸产生和ATP水平。细胞计数 Kit-8 (CCK8)、5'-ethynyl-2'-deoxyuridine (EdU) 和流式细胞仪分别用于检测细胞增殖和凋亡。通过transwell和伤口愈合测定检测迁移和侵入能力。circHMCU、miR-4458 和 PGK1 之间的关系通过双荧光素酶报告分析验证。通过动物研究评估了 circHMCU 在肿瘤生长中的功能。CircHMCU 在 BC 组织和细胞系中上调，而 miR-4458 下调。对于生物学实验，circHMCU敲低抑制细胞增殖、迁移、糖酵解，同时促进细胞凋亡。CircHMCU 结合 miR-4458，而 miR-4458 靶向 PGK1。MiR-4458 抑制逆转了 circHMCM 敲低介导的对 BC 细胞恶性行为的影响。MiR-4458 过表达抑制细胞糖酵解、增殖和转移，并通过 PGK1 上调促进 BC 细胞凋亡。此外，circHMCU 在体内抑制了肿瘤生长。CircHMCU 通过调节 BC 中的 miR-4458/PGK1 轴作为致癌因子。同时促进细胞凋亡。CircHMCU 结合 miR-4458，而 miR-4458 靶向 PGK1。MiR-4458 抑制逆转了 circHMCM 敲低介导的对 BC 细胞恶性行为的影响。MiR-4458 过表达抑制细胞糖酵解、增殖和转移，并通过 PGK1 上调促进 BC 细胞凋亡。此外，circHMCU 在体内抑制了肿瘤生长。CircHMCU 通过调节 BC 中的 miR-4458/PGK1 轴作为致癌因子。同时促进细胞凋亡。CircHMCU 结合 miR-4458，而 miR-4458 靶向 PGK1。MiR-4458 抑制逆转了 circHMCM 敲低介导的对 BC 细胞恶性行为的影响。MiR-4458 过表达抑制细胞糖酵解、增殖和转移，并通过 PGK1 上调促进 BC 细胞凋亡。此外，circHMCU 在体内抑制了肿瘤生长。CircHMCU 通过调节 BC 中的 miR-4458/PGK1 轴作为致癌因子。