MicroRNA-128 promotes apoptosis in lung cancer by directly targeting NIMA-related kinase 2.
MicroRNA-128 promotes apoptosis in lung cancer by directly targeting NIMA-related kinase 2.
复制标题
MicroRNA-128通过直接靶向NIMA相关激酶2促进肺癌细胞凋亡
DOI：
10.1111/1759-7714.12442
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发表时间：
2017-07
期刊：
影响因子：
2.9
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Zhao D;Han W;Liu X;Cui D;Chen Y
MicroRNA-128（miR-128）通过介导不同的靶点诱导癌细胞凋亡、分化、上皮向间质转化过程和肿瘤生长，作为调节剂。NIMA相关激酶2（NEK 2）在肺癌中异常表达。据报道，miR-128/NEK 2通路可预测结直肠癌的预后;然而，确定肺癌中miR-128和NEK 2之间的关系仍然难以捉摸。我们探索了miR-128和NEK 2在肺癌中的相关性。通过真实的时间PCR检测15例肺癌组织中miR-128和NEK 2的表达。用miR-128模拟物、抑制剂或阴性对照转染肺癌SK-MES-1细胞。采用定量真实的时间PCR和Western blot检测miR-128和NEK 2表达水平。通过流式细胞术进行SK‐MES‐1细胞凋亡。与邻近的非肿瘤组织相比，15例肺癌组织中miR-128下调，NEK 2上调。转染miR-128模拟物的肺癌SK-MES-1细胞诱导的凋亡率高于转染阴性对照的细胞。双荧光素酶实验进一步证实了NEK 2是miR-128在肺癌中的直接靶点，转染miR-128模拟物可降低NEK 2蛋白水平，而miR-128抑制剂可增加NEK 2表达。最后，miR-128模拟物诱导的肺癌细胞凋亡效应可被NEK 2过表达逆转。 肺癌中NEK 2受miR-128调控，miR-128通过介导NEK 2表达诱导肺癌细胞凋亡。
MicroRNA‐128 (miR‐128) serves as a regulator by inducing cancer cell apoptosis, differentiation, the epithelial‐to‐mesenchymal transition process, and tumor growth by mediating different targets. NIMA‐related kinase 2 (NEK2) is aberrantly expressed in lung cancer. The miR‐128/NEK2 pathway has been reported to predict prognosis in colorectal cancer; however, the determination of a relationship between miR‐128 and NEK2 in lung cancer has remained elusive. We explored the association between miR‐128 and NEK2 in lung cancer. MiR‐128 and NEK2 expression were examined in 15 lung cancer tissues by real time‐PCR. Lung cancer SK‐MES‐1 cells were transfected with miR‐128 mimic, an inhibitor or a negative control. MiR‐128 and NEK2 expression levels were detected using quantitative real time‐PCR and Western blot. SK‐MES‐1 cell apoptosis was performed by flow cytometry. Compared to adjacent non‐tumor tissues, miR‐128 was downregulated and NEK2 was upregulated in 15 lung cancer tissues. Lung cancer SK‐MES‐1 cells transfected with miR‐128 mimic induced a higher apoptotic rate than those transfected with the negative control. Dual luciferase assay further confirmed that NEK2 was a direct target of miR‐128 in lung cancer, and transfection with miR‐128 mimic could decrease the NEK2 protein level while the miR‐128 inhibitor increased NEK2 expression. Finally, the apoptotic effect of lung cancer cells induced by miR‐128 mimic could be reversed by NEK2 overexpression. NEK2 was regulated by miR‐128 in lung cancer and miR‐128 induced lung cancer cell apoptosis by mediating NEK2 expression.