期刊
PLOS ONE
卷 7, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0047449
关键词
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资金
- National Cancer Center Grant of South Korea [1010171, 1010172, 1110110, 1210043-1, 1210320-1, 1210042-1]
- Basic Science Research Program through the National Research Foundation of Korea
- Ministry of Education, Science, and Technology [2009-0089971]
- Korea Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea [A110878]
- National Research Foundation Grant of South Korea [2012-0008362]
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [1230920-1]
- Korea Health Promotion Institute [1210043-1, 1110110, 1210042-1, 1210320-1, A110878] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2009-0089971] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Radiation is a core part of therapy for malignant glioma and is often provided following debulking surgery. However, resistance to radiation occurs in most patients, and the underlying molecular mechanisms of radio-resistance are not fully understood. Here, we demonstrated that microRNA 21 (miR-21), a well-known onco-microRNA in malignant glioma, is one of the major players in radio-resistance. Radio-resistance in different malignant glioma cell lines measured by cytotoxic cell survival assay was closely associated with miR-21 expression level. Blocking miR-21 with anti-miR-21 resulted in radio-sensitization of U373 and U87 cells, whereas overexpression of miR-21 lead to a decrease in radio-sensitivity of LN18 and LN428 cells. Anti-miR-21 sustained gamma-H2AX DNA foci formation, which is an indicator of double-strand DNA damage, up to 24 hours and suppressed phospho-Akt (ser473) expression after exposure to c-irradiation. In a cell cycle analysis, a significant increase in the G(2)/M phase transition by anti-miR-21 was observed at 48 hours after irradiation. Interestingly, our results showed that anti-miR-21 increased factors associated with autophagosome formation and autophagy activity, which was measured by acid vesicular organelles, LC3 protein expression, and the percentage of GFP-LC3 positive cells. Furthermore, augmented autophagy by anti-miR-21 resulted in an increase in the apoptotic population after irradiation. Our results show that miR-21 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy and provide a novel phenomenon for the acquisition of radio-resistance.
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