並列タイトル等APOBEC3Gの機能阻害によるγ線に対する放射線増感
タイトル（掲載誌）International Journal of Molecular Sciences
授与機関名Nagasaki University (長崎大学)
一般注記The radiosensitization of tumor cells is one of the promising approaches for enhancing radiation damage to cancer cells and limiting radiation effects on normal tissue. In this study, we performed a comprehensive screening of radiosensitization targets in human lung cancer cell line A549 using an shRNA library and identified apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G: A3G) as a candidate target. APOBEC3G is an innate restriction factor that inhibits HIV-1 infection as a cytidine deaminase. APOBEC3G knockdown with siRNA showed an increased radiosensitivity in several cancer cell lines, including pancreatic cancer MIAPaCa2 cells and lung cancer A549 cells. Cell cycle analysis revealed that APOBEC3G knockdown increased S-phase arrest in MIAPaCa2 and G2/M arrest in A549 cells after γ-irradiation. DNA double-strand break marker γH2AX level was increased in APOBEC3G-knocked-down MIAPaCa2 cells after γ-irradiation. Using a xenograft model of A549 in mice, enhanced radiosensitivity by a combination of X-ray irradiation and APOBEC3G knockdown was observed. These results suggest that the functional inhibition of APOBEC3G sensitizes cancer cells to radiation by attenuating the activation of the DNA repair pathway, suggesting that APOBEC3G could be useful as a target for the radiosensitization of cancer therapy.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1505号 学位授与年月日:令和5年3月20日
Author: Ying Tong, Sota Kikuhara, Takae Onodera, Lichao Chen, Aung Bhone Myat, Shoji Imamichi, Yuka Sasaki, Yasufumi Murakami, Tadashige Nozaki, Hiroaki Fujimori, Mitsuko Masutani
Citation: International Journal of Molecular Sciences, 23(9), art. no. 5069; 2022
identifier:Nagasaki University (長崎大学), 博士(医学) (2023-03-20)
機関リポジトリ記載の権利情報: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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