MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells.
MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells.
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DOI：
10.1038/s41417-018-0050-1
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发表时间：
2019-09
影响因子：
6.4
通讯作者：
Kwon T
中科院分区：
文献类型：
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作者：
Chandimali N;Huynh DL;Zhang JJ;Lee JC;Yu DY;Jeong DK;Kwon T
先前，我们证明了Prx II对吉非替尼耐药A549 （A549/GR）细胞系的存活很重要，A549/GR是一种通过反复暴露于吉非替尼衍生的非小细胞肺癌细胞系。因此，在本研究中，我们使用A549/GR细胞来研究Prx II在GR NSCLC干细胞性中的作用。首先，为了探索A549/GR细胞的干性特征，并研究Prx II与这些干性特征的关系，我们成功地从A549/GR细胞中分离出一个干细胞样群体。A549/GR CD133+细胞具有重要的癌症干性特征，包括转移、血管生成、自我更新、表达干性基因和上皮-间质转化（EMT）标记物的能力。然而，这些特征通过敲低Prx II的表达而被消除。MicroRNA 122 （miR-122）在A549/GR癌症干细胞（CSCs）中靶向Prx II，从而在体外和体内抑制干细胞特性。接下来，我们研究miR-122过表达是否与Prx-II表达和Prx-II诱导的干细胞特性相关，我们将miR-122转染到A549/GR CSCs中。MiR-122通过下调Hedgehog、Notch和Wnt/β-catenin通路抑制A549/GR的干性。综上所述，我们的数据表明Prx II促进了A549/GR的干细胞性，靶向Prx II和miR-122是GR nsclc抗癌干细胞治疗的潜在可行策略。
Previously, we demonstrated that Prx II is important for survival of the gefitinib-resistant A549 (A549/GR) cell line, an NSCLC cell line derived by repeated exposure to gefitinib. Therefore, in this study, we used A549/GR cells to investigate the role of Prx II in GR NSCLC stemness. Initially, to explore the stemness characteristics and investigate the association of Prx II with those stemness characteristics, we successfully isolated a stem cell-like population from A549/GR cells. A549/GR CD133+ cells possessed important cancer stemness characteristics, including the abilities to undergo metastasis, angiogenesis, self-renewal, and to express stemness genes and epithelial–mesenchymal transition (EMT) markers. However, those characteristics were abolished by knocking down Prx II expression. MicroRNA 122 (miR-122) targets Prx II in A549/GR cancer stem cells (CSCs), thereby inhibiting the stemness characteristics in vitro and in vivo. Next, we investigate whether miR-122 overexpression was associated with Prx II expression and Prx-II-induced stemness characteristics, we transfected miR-122 into A549/GR CSCs. MiR-122 inhibited A549/GR stemness by downregulating the Hedgehog, Notch, and Wnt/β-catenin pathways. Taken together, our data suggest that Prx II promotes A549/GR stemness, and that targeting Prx II and miR-122 is a potentially viable strategy for anti-cancer-stem cell therapy in GR NSCLCs.
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影响因子：
16.6
作者：
Cai J;Fang L;Huang Y;Li R;Xu X;Hu Z;Zhang L;Yang Y;Zhu X;Zhang H;Wu J;Huang Y;Li J;Zeng M;Song E;He Y;Zhang L;Li M
通讯作者：
Li M
影响因子：
4.6
作者：
Jin D;Lee H
通讯作者：
Lee H
影响因子：
5.6
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Ma D;Jia H;Qin M;Dai W;Wang T;Liang E;Dong G;Wang Z;Zhang Z;Feng F
通讯作者：
Feng F
影响因子：
3.4
作者：
Diao, Shu;Zhang, Jin-fang;Kung, Hsiang-fu
通讯作者：
Kung, Hsiang-fu
影响因子：
12.4
作者：
通讯作者：
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