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  • [Mol Ther.] LDR-유도/PAI-1-표적 miRNA에 의한 NSCLC 방사선치료효율 증대 연구LDR-Induced miR-30a and miR-30b Target the PAI-1 Pathway to Control Adverse Effects of NSCLC Radiotherapy.

    부산대 / 박가을, 손범석, 강지훈, 윤부현*

  • 출처
    Mol Ther.
  • 등재일
    2019 Feb 6
  • 저널이슈번호
    27(2):342-354. doi: 10.1016/j.ymthe.2018.10.015. Epub 2018 Oct 26.
  • 내용

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    Abstract
    Radiotherapy has been a central part in curing non-small cell lung cancer (NSCLC). However, it is possible that not all of the tumor cells are destroyed by radiation; therefore, it is important to effectively control residual tumor cells that could become aggressive and resistant to radiotherapy. In this study, we aimed to investigate the molecular mechanism of decreased NSCLC radioresistance by low-dose radiation (LDR) pretreatment. The results indicated that miR-30a and miR-30b, which effectively inhibited plasminogen activator inhibitor-1 (PAI-1), were overexpressed by treatment of LDR to NSCLC cells. Phosphorylation of Akt and ERK, the downstream survival signals of PAI-1, was decreased by PAI-1 inhibition. Reduced cell survival and epithelial-mesenchymal transition by PAI-1 inhibition were confirmed in NSCLC cells. Moreover, in vivo orthotopic xenograft mouse models with 7C1 nanoparticles to deliver miRNAs showed that tumor growth and aggressiveness were efficiently decreased by LDR treatment followed by radiotherapy. Taken together, the present study suggested that PAI-1, whose expression is regulated by LDR, was critical for controlling surviving tumor cells after radiotherapy.

     


    Author information

    Park G1, Son B1, Kang J2, Lee S1, Jeon J3, Kim JH4, Yi GR5, Youn H6, Moon C7, Nam SY8, Youn B9.
    1
    Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea.
    2
    Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea; Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
    3
    Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea; Department of Radiation Oncology, Haeundae Paik Hospital, Inje University School of Medicine, Busan 48108, Republic of Korea.
    4
    Department of Chemistry, Molecular Design Institute, New York University, New York, NY 10003, USA.
    5
    School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
    6
    Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
    7
    Department of Veterinary Anatomy, College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
    8
    Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.
    9
    Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea; Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea. Electronic address: bhyoun72@pusan.ac.kr.

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