MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling.
MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling.
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DOI：
10.18632/oncotarget.18924
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Kim IA
中科院分区：
文献类型：
--
作者：
Koo T;Cho BJ;Kim DH;Park JM;Choi EJ;Kim HH;Lee DJ;Kim IA
最近发现microRNA-200 c（miR-200 c）通过抑制几种癌症中的上皮-间质转化（EMT）而具有肿瘤抑制特性。miR-200 c还与多种细胞信号分子相互作用，调节许多重要的信号通路。在这项研究中，我们研究了miR-200 c在一组人癌细胞系中的放射增敏作用及其机制。恶性胶质瘤（U251，T98 G）、乳腺癌（MDA-MB-468）和肺癌（A549）细胞用对照前体微RNA、前体miR-200 c或抗miR-200 c转染。然后进行RT-PCR、克隆形成试验、免疫印迹和免疫细胞化学。为了预测miR-200 c的潜在靶点，使用microRNA数据库进行生物信息学分析。miR-200 c的异位过表达下调了p-EGFR和p-AKT，并增加了U251、T98 G、A549和MDA-MB-468细胞的放射敏感性。相反，miR-200 c抑制上调p-EGFR和p-AKT，并减少辐射诱导的细胞杀伤。miR-200 c导致持续的γ H2 AX灶形成并下调pDNA-PKC表达。自噬和凋亡是细胞死亡的主要方式。生物信息学分析预测miR-200 c可能与EGFR、AKT 2、MAPK 1、VEGFA和HIF 1AN相关。我们还证实了miR-200 c下调了U251和A549细胞中VEGF、HIF-1α和MMP 2的表达。在这些细胞中，过表达miR-200 c抑制了侵袭、迁移和血管形成。这些表型变化与E-cadherin和EphA 2下调和N-cadherin上调相关。miR-200 c对正常人成纤维细胞和星形胶质细胞没有观察到细胞毒性作用。总之，我们的数据表明，miR-200 c是一个有吸引力的目标，通过独特的调节控制癌症促生存信号和EMT的复杂调控网络，提高放射治疗的疗效。
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c. Then, RT-PCR, clonogenic assays, immunoblotting, and immunocytochemisty were performed. To predict the potential targets of miR-200c, microRNA databases were used for bioinformatics analysis. Ectopic overexpression of miR-200c downregulated p-EGFR and p-AKT and increased the radiosensitivity of U251, T98G, A549, and MDA-MB-468 cells. In contrast, miR-200c inhibition upregulated p-EGFR and p-AKT, and decreased radiation-induced cell killing. miR-200c led to persistent γH2AX focus formation and downregulated pDNA-PKc expression. Autophagy and apoptosis were major modes of cell death. Bioinformatics analysis predicted that miR-200c may be associated with EGFR, AKT2, MAPK1, VEGFA, and HIF1AN. We also confirmed that miR-200c downregulated the expression of VEGF, HIF-1α, and MMP2 in U251 and A549 cells. In these cells, overexpressing miR-200c inhibited invasion, migration, and vascular tube formation. These phenotypic changes were associated with E-cadherin and EphA2 downregulation and N-cadherin upregulation. miR-200c showed no observable cytotoxic effect on normal human fibroblasts and astrocytes. Taken together, our data suggest that miR-200c is an attractive target for improving the efficacy of radiotherapy via a unique modulation of the complex regulatory network controlling cancer pro-survival signaling and EMT.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
6.4
作者：
Chetty, Chandramu;Lakka, Sajani S.;Bhoopathi, Praveen;Rao, Jasti S.
通讯作者：
Rao, Jasti S.
癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
乳腺癌细胞迁移和侵袭过程中 miRNA:mRNA 相互作用的系统评估
影响因子：
7.4
作者：
Luo D;Wilson JM;Harvel N;Liu J;Pei L;Huang S;Hawthorn L;Shi H
通讯作者：
Shi H
影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.