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  • Title: eEF-2 Kinase-targeted miR-449b confers radiation sensitivity to cancer cells.
    Author: Ji C, Xu Q, Guo L, Wang X, Ren Y, Zhang H, Zhu W, Ming Z, Yuan Y, Ren X, Song J, Cheng Y, Yang J, Zhang Y.
    Journal: Cancer Lett; 2018 Apr 01; 418():64-74. PubMed ID: 29331413.
    Abstract:
    The roles of microRNA in regulation of various biological processes and in modulation of therapeutic effects have been widely appreciated. In this study, we found a positive correlation between miR-449 b expression and radiation sensitivity in cancer cells and in tumor specimens from patients. We showed that eEF-2 kinase, a negative regulator of global protein synthesis, is a target of miR-449 b. Introducing a miR-449 b mimic into cancer cells led to suppression of eEF-2 kinase expression, leading to increases of protein synthesis and depletion of cellular ATP. Further, we demonstrated that the miR-449 b mimic rendered the cancer cells more sensitive to ionizing radiation both in vitro (cell culture) and in vivo (animal xenograft model). Moreover, the radiation sensitivity conferred by miR-449 b could be blunted by cycloheximide, an inhibitor of protein synthesis, or by direct delivery of ATP liposome, supporting eEF-2 kinase as a mediator of the radio-sensitizing effects of miR-449 b. These results indicate that miR-449 b, which is frequently down-regulated in radio-resistant cancers, may represent a new critical determinant of radio-sensitivity.
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