Department of General Surgery I, Guiyang Hospital of Guizhou Aviation Industry Group, Guiyang, China.
Department of Orthopedics (Spine group), Guiyang Hospital of Guizhou Aviation Industry Group, Guiyang, China.
Cancer Biother Radiopharm. 2021 Aug;36(6):477-490. doi: 10.1089/cbr.2019.3389. Epub 2020 Jun 9.
Breast cancer (BC) is a common tumor in women worldwide, and irradiation (IR) resistance is a major obstacle for BC therapy. Circle RNAs (circRNAs) were identified as implicated in the progression of cancer and IR resistance. However, the role of circABCB10 in BC progression and IR resistance is not well defined. The levels of circABCB10, miR-223-3p, and profilin-2 (PFN2) were detected by quantitative real-time polymerase chain reaction. The cell viability and survival rate were monitored by MTT assay. The glucose consumption, lactic acid production, LDH-A activity, and ATP production were evaluated to measure glycolysis. The protein levels of hypoxia inducible factor-1α (HIF-1α), hexokinase 2 (HK2), lactate dehydrogenase A chain (LDH-A), and PFN2 were estimated by Western blot assay. The colony formation rate was tested by colony formation assay. Dual-luciferase reporter assay was constructed to validate the interaction between miR-223-3p and circABCB10 or PFN2. The mice xenograft assay was performed to further verify the effects of circABCB10 on BC progression . CircABCB10 and PFN2 were elevated, while miR-223-3p was reduced in BC tissues and cells. CircABCB10 sponged miR-223-3p, and PFN2 was a target of miR-223-3p in BC cells. CircABCB10 silencing inhibited cell proliferation, glycolysis, colony formation, and decreased IR resistance in BC cells by modulating miR-223-3p. Meanwhile, circABCB10 depletion restrained xenograft tumor growth . Also, miR-223-3p overexpression refrained cell proliferation, glycolysis, and colony formation while improving IR sensitivity in BC cells by regulating PFN2. Besides, circABCB10 knockdown declined PFN2 in BC cells via miR-223-3p. The glycolysis inhibitor 2-deoxy-D-glucose enhanced IR sensitivity in BC cells via circABCB10. CircABCB10 knockdown contributed to irradiation sensitivity by negatively regulating glycolysis via the miR-223-3p/PFN axis in breast cancer.
乳腺癌(BC)是全球女性中常见的肿瘤,辐射(IR)抵抗是 BC 治疗的主要障碍。环状 RNA(circRNA)被认为与癌症的进展和 IR 抵抗有关。然而,circABCB10 在 BC 进展和 IR 抵抗中的作用尚不清楚。通过实时定量聚合酶链反应检测 circABCB10、miR-223-3p 和 Profilin-2(PFN2)的水平。通过 MTT 测定法监测细胞活力和存活率。通过评估葡萄糖消耗、乳酸生成、LDH-A 活性和 ATP 产生来测量糖酵解。通过 Western blot 测定法估计缺氧诱导因子-1α(HIF-1α)、己糖激酶 2(HK2)、乳酸脱氢酶 A 链(LDH-A)和 PFN2 的蛋白水平。通过集落形成测定法测试集落形成率。构建双荧光素酶报告基因实验验证 miR-223-3p 与 circABCB10 或 PFN2 的相互作用。进行小鼠异种移植实验进一步验证 circABCB10 对 BC 进展的影响。circABCB10 和 PFN2 升高,而 miR-223-3p 在 BC 组织和细胞中降低。circABCB10 海绵吸附 miR-223-3p,PFN2 是 BC 细胞中 miR-223-3p 的靶标。circABCB10 沉默通过调节 miR-223-3p 抑制 BC 细胞的增殖、糖酵解、集落形成并降低 BC 细胞的 IR 抵抗。同时,circABCB10 耗竭通过 miR-223-3p 抑制异种移植肿瘤生长。此外,miR-223-3p 过表达通过调节 PFN2 抑制 BC 细胞的增殖、糖酵解和集落形成,同时提高 BC 细胞的 IR 敏感性。此外,circABCB10 沉默通过 miR-223-3p 降低 BC 细胞中的 PFN2。糖酵解抑制剂 2-脱氧-D-葡萄糖通过 circABCB10 负调控糖酵解增强 BC 细胞的 IR 敏感性。circABCB10 通过负调控 miR-223-3p/PFN 轴在乳腺癌中负调节糖酵解,有助于辐照敏感性。