Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Xiangyin Road, Shanghai 200433, PR China.
J Cell Biochem. 2013 Mar;114(3):606-15. doi: 10.1002/jcb.24398.
Due to the intrinsic resistance of many tumors to radiotherapy, current methods to improve the survival of cancer patients largely depend on increasing tumor radiosensitivity. It is well-known that miR-200c inhibits epithelial-mesenchymal transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify the effects of miR-200c on the radiosensitization of human breast cancer cells. In this study, we found that low levels of miR-200c expression correlated with radiotolerance in breast cancer cells. miR-200c overexpression could increase radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double-strand breaks. Additionally, we found that miR-200c directly targeted TANK-binding kinase 1 (TBK1). However, overexpression of TBK1 partially rescued miR-200c mediated apoptosis induced by ionizing radiation. In summary, miR-200c can be a potential target for enhancing the effect of radiation treatment on breast cancer cells.
由于许多肿瘤对放疗具有内在的抗性，目前提高癌症患者生存率的方法主要依赖于提高肿瘤的放射敏感性。众所周知，miR-200c 抑制上皮-间充质转化（EMT），并增强癌细胞的化疗敏感性。我们试图阐明 miR-200c 对人乳腺癌细胞放射增敏的作用。在这项研究中，我们发现 miR-200c 表达水平低与乳腺癌细胞的放射耐受性相关。miR-200c 的过表达可以通过抑制细胞增殖，增加细胞凋亡和 DNA 双链断裂，从而增加乳腺癌细胞的放射敏感性。此外，我们发现 miR-200c 可以直接靶向 TANK 结合激酶 1（TBK1）。然而，TBK1 的过表达部分挽救了 miR-200c 介导的电离辐射诱导的细胞凋亡。总之，miR-200c 可以成为增强放射治疗对乳腺癌细胞效果的潜在靶点。
