Department of Breast Cancer, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Breast Cancer, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Cell Signal. 2021 Mar;79:109878. doi: 10.1016/j.cellsig.2020.109878. Epub 2020 Dec 9.
Circular RNAs (circRNAs) are implicated in the initiation and advancement of diverse tumors. CircRNA hsa_circ_0069094 (circ_0069094) has been reported to be upregulated in BC, but the biological role of circ_0069094 in BC is indistinct. Hence, we aimed to survey the biological role of circ_0069094 in BC. In the present study, we verified that circ_0069094 was upregulated in BC tissues and cells. BC patients with high circ_0069094 expression had a poor prognosis. Functional analysis revealed that circ_0069094 silencing induced apoptosis, curbed proliferation, and reduced glycolysis in BC cells in vitro, but circ_0069094 overexpression had an opposing influence. Also, circ_0069094 knockdown reduced BC growth in vivo. Mechanically, circ_0069094 was validated as a decoy for miR-591, which targeted HK2. Importantly, circ_0069094 sponged miR-591 to regulate HK2 expression. Both miR-591 silencing and HK2 overexpression counteracted circ_0069094 inhibition-mediated influence on cell proliferation, apoptosis, and glycolysis in BC cells. In conclusion, these results indicated that circ_0069094 facilitated cell malignancy and glycolysis by upregulating HK2 through adsorbing miR-591, suggesting that circ_0069094 might be a prognostic biomarker and therapeutic target for BC.
环状 RNA（circRNAs）参与多种肿瘤的发生和发展。已有报道称 circRNA hsa_circ_0069094（circ_0069094）在 BC 中上调，但 circ_0069094 在 BC 中的生物学作用尚不清楚。因此，我们旨在研究 circ_0069094 在 BC 中的生物学作用。在本研究中，我们验证了 circ_0069094 在 BC 组织和细胞中上调。circ_0069094 高表达的 BC 患者预后不良。功能分析显示，circ_0069094 沉默在体外诱导 BC 细胞凋亡、抑制增殖和降低糖酵解，而 circ_0069094 过表达则产生相反的影响。此外，circ_0069094 下调抑制了 BC 在体内的生长。机制上，circ_0069094 被验证为 miR-591 的诱饵，miR-591 靶向 HK2。重要的是，circ_0069094 吸附 miR-591 调节 HK2 表达。miR-591 沉默和 HK2 过表达均能拮抗 circ_0069094 抑制介导的对 BC 细胞增殖、凋亡和糖酵解的影响。综上所述，这些结果表明，circ_0069094 通过吸附 miR-591 上调 HK2 促进细胞恶性和糖酵解，提示 circ_0069094 可能是 BC 的预后标志物和治疗靶点。
