Silencing miR-21 sensitizes non-small cell lung cancer A549 cells to ionizing radiation through inhibition of PI3K/Akt.
Silencing miR-21 sensitizes non-small cell lung cancer A549 cells to ionizing radiation through inhibition of PI3K/Akt.
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DOI：
10.1155/2014/617868
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发表时间：
2014
影响因子：
--
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Ma Y;Xia H;Liu Y;Li M
我们研究了microRNA-21(miR-21)在非小细胞肺癌(NSCLC)放疗耐药中的作用及其分子机制。将抗miR-21基因和阴性对照寡核苷酸分别导入A549细胞，实时定量聚合酶链式反应检测miR-21基因的表达水平。采用克隆形成生存分析、四甲基偶氮唑盐比色法、流式细胞术和Western blotting检测电离辐射后A549细胞的存活分数、增殖、凋亡和磷酸化Akt的表达。放射抗性NSCLC A549细胞miR-21表达下调可抑制IR后A549细胞的集落形成和增殖。此外，沉默miR-21增强了IR诱导的A549细胞的凋亡，并伴随着磷酸化Akt蛋白水平的降低。然而，PI3K激活剂IGF-1逆转了miR-21基因敲除引起的A549细胞IR后对磷酸化Akt蛋白水平的抑制和对细胞凋亡的促进作用。在耐受辐射的NSCLC A549细胞中沉默miR-21，通过抑制PI3K/Akt信号通路，抑制细胞增殖，促进细胞凋亡，从而使其对IR敏感。这可能有助于非小细胞肺癌对放射治疗的增敏。
We investigated the role of microRNA-21 (miR-21) in radiotherapy resistance of non-small cell lung cancers (NSCLC) and the underlying molecular mechanism. A549 cells were transfected with anti-miR-21 or the negative control oligonucleotides and real-time PCR was applied to detect miR-21 expression level. After ionizing radiation (IR), the survival fractions, proliferation, apoptosis, and expression of phosphorylated-Akt of A549 cells were determined by clonogenic survival analysis, MTT assay, flow cytometry, and Western blotting. Downregulation of miR-21 in radioresistant NSCLC A549 cells inhibited the colony-forming ability and proliferation of A549 cells after IR. Moreover, silencing miR-21 enhanced apoptosis of A549 cells induced by IR accompanied by decreased phosphorylated-Akt protein level. However, PI3K activator IGF-1 reversed suppression of phosphorylated-Akt protein level and promotion of apoptosis of A549 cells after IR caused by miR-21 knockdown. Silencing miR-21 in radioresistant NSCLC A549 cells sensitized them to IR by inhibiting cell proliferation and enhancing cell apoptosis through inhibition of PI3K/Akt signaling pathway. This might help in sensitization of NSCLC to radiotherapy.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
4.3
作者：
Li, Si;Liang, Zhu;Zou, Fangdong
通讯作者：
Zou, Fangdong
影响因子：
3.6
作者：
Provencio, Mariano;Sanchez, Antonio;Valcarcel, Francisco
通讯作者：
Valcarcel, Francisco
影响因子：
7.3
作者：
Farazi, Thalia A.;Spitzer, Jessica I.;Morozov, Pavel;Tuschl, Thomas
通讯作者：
Tuschl, Thomas
影响因子：
5.8
作者：
Griveau, A.;Bejaud, J.;Garcion, E.
通讯作者：
Garcion, E.