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miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells

  • Original Article
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Tumor Biology

Abstract

miR-449a, a novel tumor suppressor, is deregulated in various malignancies, including prostate cancer. Overexpression of miR-449a induces cell cycle arrest, apoptosis, and senescence, but its role in response to ionizing radiation and underlying molecular mechanism are still unknown. Here, we report that miR-449a enhances radiation-induced G2/M phase arrest and apoptosis through modulating pRb/E2F1 and sensitizes prostate cancer cells to X-ray radiation. In wild-type Rb PC-3 cells, overexpression of miR-449a enhances radiation-induced G2/M arrest and apoptosis and promotes the sensitivity to X-ray radiation. While mutant Rb DU-145 cells are resistant to the X-ray radiation despite in the presence of miR-449a. The cell cycle distribution of DU-145 cells is not significantly altered by miR-449a in the response to ionizing radiation. Furthermore, elevated miR-449a downregulates cell cycle regulator CDC25A and oncogene HDAC1. By targeting genes involved in controlling pRb/E2F1 activity, miR-449a regulates cell cycle progression and apoptosis and consequently enhances the radiosensitivity of PC-3 cells. Thus, miR-449a, as a miRNA component of the Rb pathway, promotes the radiosensitivity of PC-3 cells through regulating pRb/E2F1.

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Acknowledgments

This work was supported by the grants from the Key program of National Natural Science Foundation of China (U1432248), the National Natural Science Foundation of China (11105203 and 11405230), and the Scientific Technology Research Projects of Gansu Province (1107RJYA033).

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Authors and Affiliations

  1. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China

    Aihong Mao, Yang Liu, Yali Wang, Qiuyue Zhao, Xin Zhou, Chao Sun, Cuixia Di, Jing Si, Lu Gan & Hong Zhang

  2. School of Nuclear Science and Technology, Lanzhou University, Lanzhou, 730000, China

    Aihong Mao

  3. Institute of Gansu Medical Science Research, Lanzhou, 730050, China

    Aihong Mao

  4. Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China

    Yang Liu, Yali Wang, Qiuyue Zhao, Xin Zhou, Chao Sun, Cuixia Di, Jing Si, Lu Gan & Hong Zhang

  5. Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, 730000, China

    Yang Liu, Yali Wang, Qiuyue Zhao, Xin Zhou, Chao Sun, Cuixia Di, Jing Si, Lu Gan & Hong Zhang

  6. University of Chinese Academy of Sciences, Beijing, 100039, China

    Aihong Mao & Qiuyue Zhao

  7. Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, 730000, China

    Hong Zhang

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  1. Aihong Mao
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  2. Yang Liu
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Correspondence to Hong Zhang.

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Yang Liu joint first author.

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Mao, A., Liu, Y., Wang, Y. et al. miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells. Tumor Biol. 37, 4831–4840 (2016). https://doi.org/10.1007/s13277-015-4336-8

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  • DOI: https://doi.org/10.1007/s13277-015-4336-8

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