Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China.
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, PR China.
Biochem Biophys Res Commun. 2019 Apr 30;512(2):392-398. doi: 10.1016/j.bbrc.2019.03.082. Epub 2019 Mar 20.
Radioresistance is a major challenge in lung cancer radiotherapy (RT), and consequently, new radiosensitizers are urgently needed. MicroRNAs (miRNAs) have been demonstrated to participate in many important cellular processes including radiosensitization. MiR-365 is dysregulated in non-small cell lung cancer (NSCLC) and is able to restrain the development of NSCLC. However, the relationship between miR-365 and radiosensitivities of NSCLC cells remains largely unknown. Here we reveal that overexpression of miR-365 is able to enhance the radiosensitivity of NSCLC cells through targeting CDC25A. We found that the expression level of miR-365 was positively correlated with the radiosensitivity of NSCLC cell lines. Furthermore, our results showed that overexpression of miR-365 could sensitize A549 cells to the irradiation. However, knockdown of miR-365 in H460 cells could act the converse manner. Mechanically, miR-365 was able to directly target 3'UTR of cell division cycle 25A (CDC25A) mRNA and reduce the expression of CDC25A at the levels of mRNA and protein. And we confirmed that miR-365 could increase the radiosensitivity of NSCLC cells by targeting CDC25A using in vitro and in vivo assays. Taken together, restoration of miR-365 expression enhances the radiosensitivity of NSCLC cells by suppressing CDC25A, and miR-365 could be used as a radiosensitizer for NSCLC therapy.
放射抵抗是肺癌放射治疗（RT）的主要挑战，因此，迫切需要新的放射增敏剂。microRNAs（miRNAs）已被证明参与许多重要的细胞过程，包括放射增敏。miR-365 在非小细胞肺癌（NSCLC）中失调，能够抑制 NSCLC 的发展。然而，miR-365 与 NSCLC 细胞的放射敏感性之间的关系在很大程度上尚不清楚。在这里，我们揭示了过表达 miR-365 通过靶向 CDC25A 能够增强 NSCLC 细胞的放射敏感性。我们发现 miR-365 的表达水平与 NSCLC 细胞系的放射敏感性呈正相关。此外，我们的结果表明，过表达 miR-365 可以使 A549 细胞对辐射敏感。然而，在 H460 细胞中敲低 miR-365 则可以产生相反的效果。在机制上，miR-365 能够直接靶向细胞分裂周期 25A（CDC25A）mRNA 的 3'UTR，并降低 CDC25A mRNA 和蛋白水平的表达。并且我们通过体外和体内实验证实了 miR-365 可以通过靶向 CDC25A 增加 NSCLC 细胞的放射敏感性。总之，恢复 miR-365 的表达通过抑制 CDC25A 增强 NSCLC 细胞的放射敏感性，miR-365 可用于 NSCLC 的放射治疗。
