Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Department of Pharmacy, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 215028, China.
Biochem Biophys Res Commun. 2021 Oct 8;573:19-26. doi: 10.1016/j.bbrc.2021.08.014. Epub 2021 Aug 6.
As a common treatment of human glioma, ionizing radiation (IR) was reported to result in cell cycle arrest. However, the mechanisms underlying IR-induced abnormal cell cycle remain largely unclear. Here we found that IR caused an elevated expression of B-Myb and cell cycle-related proteins, as well as G2/M phase arrest in U251 cells instead of U87 cells. However, the knockdown of B-Myb by small interfering RNAs ameliorated the increasing of cell cycle-related proteins and G2/M phase arrest induced by IR. Further analysis demonstrated that decreased-B-Myb enhanced the sensitivity of U251 cells to IR. Moreover, the establishment of H1299 cell line proved that B-Myb expression was associated with the status of p53. Immunoprecipitation (IP) and chromatin immunoprecipitation (CHIP) assay results indicated that mutant p53 and SP1 regulated the expression of B-Myb via different mechanisms. This study not only elucidated the role of B-Myb in IR-induced cell cycle alternation, but also provided insight into mechanism of B-Myb expression.
作为人类神经胶质瘤的常见治疗方法，电离辐射（IR）已被报道可导致细胞周期停滞。然而，IR 诱导的异常细胞周期的机制在很大程度上仍不清楚。在这里，我们发现 IR 导致 U251 细胞而非 U87 细胞中 B-Myb 和细胞周期相关蛋白的表达升高，以及 G2/M 期阻滞。然而，小干扰 RNA 敲低 B-Myb 可改善 IR 诱导的细胞周期相关蛋白增加和 G2/M 期阻滞。进一步的分析表明，减少 B-Myb 可增强 U251 细胞对 IR 的敏感性。此外，H1299 细胞系的建立证明了 B-Myb 的表达与 p53 的状态有关。免疫沉淀（IP）和染色质免疫沉淀（CHIP）实验结果表明，突变型 p53 和 SP1 通过不同的机制调节 B-Myb 的表达。本研究不仅阐明了 B-Myb 在 IR 诱导的细胞周期改变中的作用，还深入了解了 B-Myb 表达的机制。
