MiR-873 inhibition enhances gefitinib resistance in non-small cell lung cancer cells by targeting glioma-associated oncogene homolog 1.
MiR-873 inhibition enhances gefitinib resistance in non-small cell lung cancer cells by targeting glioma-associated oncogene homolog 1.
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DOI：
10.1111/1759-7714.12830
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发表时间：
2018-10
期刊：
影响因子：
2.9
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Jin S;He J;Li J;Guo R;Shu Y;Liu P
非小细胞肺癌（NSCLC）患者的五年生存率非常低。miR-873参与肿瘤的生长、转移和分化。在此，我们确定了miR-873在NSCLC中的靶基因和影响。使用米兰达和Targetscan网站预测NSCLC中miR-873的靶基因。使用双荧光素酶报告基因测定试剂盒检查荧光素酶活性。分别通过细胞计数试剂盒-8、血管生成分析和流式细胞术分析细胞的活力、管形成和增殖。使用定量真实的时间PCR和蛋白质印迹分析评价miR-873和GLI 1的水平。在对EGFR-酪氨酸激酶抑制剂高度敏感的NSCLC细胞系（PC 9）中观察到低水平的GLI 1和高水平的miR-873。在PC 9和PC 9/GR细胞中，miR-873和GLI 1表达之间呈负相关。miR-873的抑制增强了GLI 1水平。miR-873表达被吉非替尼抑制。吉非替尼显著降低了PC 9细胞的活力、管形成和细胞数量。然而，miR-873的抑制增强了耐药性，GLI 1的敲除增强了PC 9细胞对吉非替尼的敏感性。 GLI 1是NSCLC中miR-873的靶基因。miR-873的抑制通过上调GLI 1增加NSCLC细胞的吉非替尼耐药性。这些结果表明，miR-873-GLI 1信号转导参与了NSCLC的吉非替尼耐药。
The five‐year survival rate of non‐small cell lung cancer (NSCLC) patients is very low. MiR‐873 is involved in the growth, metastasis, and differentiation of tumors. Herein, we determined the target gene and influence of miR‐873 in NSCLC. MiRanda and Targetscan websites were used to predict the target gene of miR‐873 in NSCLC. Luciferase activity was examined using a dual luciferase reporter gene assay kit. The viability, tube formation, and proliferation of cells were analyzed by cell counting kit‐8, angiogenic analysis, and flow cytometry, respectively. The levels of miR‐873 and GLI1 were evaluated using quantitative real‐time PCR and Western blot assays. Low levels of GLI1 and high levels of miR‐873 were observed in an NSCLC cell line (PC9) highly sensitive to EGFR‐tyrosine kinase inhibitors. There was a negative correlation between miR‐873 and GLI1 expression in PC9 and PC9/GR cells. The inhibition of miR‐873 enhanced GLI1 levels. MiR‐873 expression was inhibited by gefitinib. Gefitinib markedly reduced the viability, tube formation, and cell number in PC9 cells. However, suppression of miR‐873 enhanced the resistance and knockdown of GLI1 enhanced the sensitivity of PC9 cells to gefitinib. GLI1 is a target gene of miR‐873 in NSCLC. The inhibition of miR‐873 increased gefitinib resistance of NSCLC cells via the upregulation of GLI1. These results indicate that miR‐873‐GLI1 signaling is involved in gefitinib resistance in NSCLC.
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DOI：
10.3779/j.issn.1009-3419.2014.12.07
发表时间：
2014-12
期刊：
Zhongguo fei ai za zhi = Chinese journal of lung cancer
影响因子：
--
作者：
Duan X;Shi J
通讯作者：
Shi J
影响因子：
--
作者：
Chen MJ;Wu DW;Wang GC;Wang YC;Chen CY;Lee H
通讯作者：
Lee H
DOI：
10.1016/j.jtho.2018.03.020
发表时间：
2018-07
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Gajra A;Zemla TJ;Jatoi A;Feliciano JL;Wong ML;Chen H;Maggiore R;McMurray RP;Hurria A;Muss HB;Cohen HJ;Lafky J;Edelman MJ;Lilenbaum R;Le-Rademacher JG
通讯作者：
Le-Rademacher JG
影响因子：
8
作者：
Cui, J.;Yang, Y.;Zhang, C.
通讯作者：
Zhang, C.
影响因子：
4.8
作者：
Mens MMJ;Ghanbari M
通讯作者：
Ghanbari M