原创力文档silencing of microrna-21 confers radio-sensitivity through inhibition of the pi3kakt pathway and enhancing autophagy in malignant glioma cell lines沉默的microrna-21授予radio-sensitivity通过pi3kakt通路的抑制和增强自噬在恶性胶质瘤细胞系.pdfVIP
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silencing of microrna-21 confers radio-sensitivity through inhibition of the pi3kakt pathway and enhancing autophagy in malignant glioma cell lines沉默的microrna-21授予radio-sensitivity通过pi3kakt通路的抑制和增强自噬在恶性胶质瘤细胞系
Silencing of MicroRNA-21 Confers Radio-Sensitivity
through Inhibition of the PI3K/AKT Pathway and
Enhancing Autophagy in Malignant Glioma Cell Lines
1. 1. 1 1 1 2
Ho-Shin Gwak , Tae Hoon Kim , Guk Heui Jo , Youn-Jae Kim , Hee-Jin Kwak , Jong Heon Kim ,
1 1 1 1
Jinlong Yin , Heon Yoo , Seung Hoon Lee , Jong Bae Park *
1 Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea, 2 Cancer Cell and Molecular Biology Branch, Research Institute
and Hospital, National Cancer Center, Goyang, Korea
Abstract
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 c-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 G2/M phase transition by anti-miR-21 was observed at 48 hours after irradiation. Interestingly, ou
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