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    題名: Arsenic trioxide-mediated suppression of miR-182-5p is associated with potent anti-oxidant effects through up-regulation of SESN2
    作者: Lin, Liang-Ting;Liu, Shin-Yi;Leu, Jyh-Der;Chang, Chun-Yuan;Chiou, Shih-Hwa;Lee, Te-Chang;Lee, Yi-Jang
    Leu, Jyh-Der
    貢獻者: 神科所
    關鍵詞: anti-oxidant effect;arsenic trioxide;miR-182;oxidative stress;sestrin 2
    日期: 2018-03
    上傳時間: 2018-09-14 16:06:54 (UTC+8)
    摘要: Arsenic trioxide (ATO) is a traditional Chinese medicine that can induce oxidative stress for treatment of cancer cells. However, ATO may generate anti-oxidative responses to compromise the cytotoxic effect, but the underlying mechanisms remain unclear. Here we found that ATO could inhibit miR-182-5p expression in patient-derived primary S1 glioblastoma (GBM) cells accompanied by up-regulation of Sestrin-2 (SESN2) mRNA, a known anti-oxidant molecule. This phenomenon was also detected in a U87MG glioma cell line, human lung adenocarcinoma H1299 cell line and A549 cell line. Pretreatment with a free radical scavenger N-acetylcysteine (NAC) reduced the oxidative stress induced by ATO. Concomitantly, ATO mediated suppression of miR-182-5p and enhancement of SESN2 expression were also compromised. The MTT assay further showed that ATO induced cytotoxicity was enhanced by transfection of miR-182-5p mimics. Overexpression of miR-182-5p mimics significantly suppressed the expression of SENS2 and a firefly luciferase reporter gene fused to 3'- untranslated region (UTR) of SESN2 mRNA. Use of ribonucleoprotein immunoprecipitation (RNP-IP), ATO mediated suppression of miR-182-5p led to the stabilization of SESN2 mRNA as a result of Argonaute-2 (AGO2) dependent gene silencing. Furthermore, high expression of miR-182-5p and low expression of SESN2 mRNA tend to be associated with longer survival of glioma or lung cancer patients using public available gene expression datasets and online tools for prediction of clinical outcomes. Taken together, current data suggest that the miR-182-5p/SENS2 pathway is involved in ATO induced anti-oxidant responses, which may be important for the design of novel strategy for cancer treatment.
    關聯: Oncotarget, 9, 16028-16042
    PMID: 29662624
    資料類型: article
    DOI 連結: https://doi.org/10.18632/oncotarget.24678
    DOI: 10.18632/oncotarget.24678
    顯示於類別:[神經科學研究所 ] 期刊論文

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