KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis

KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis
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KCNQ1OT1 通过调节 miRNA-27b-3p/HSP90AA1 轴促进非小细胞肺癌的进展

DOI:
10.1002/jcp.27788
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发表时间:
2019-07-01
影响因子:
5.6
通讯作者:
Zhao, Kewen
Zhao, Kewen
中科院分区:
生物学2区
文献类型:
--
作者:
Dong, Zhiwu;Yang, Ping;Zhao, Kewen

文献摘要

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长的非编码RNA KCNQ1OT1参与了KCNQ1结构域内印记基因的调节。但它在癌症发生和转移中的作用在很大程度上仍然难以捉摸。在此,我们评估了它在非小细胞肺癌(NSCLC)进展中的潜力。我们发现KCNQ1OT1在非小细胞肺癌组织和细胞系中表达上调。高KCNQ1OT1水平与NSCLC患者总体和无进展生存期差相关。KCNQ1OT1促进H460细胞的增殖、迁移和侵袭。此外,KCNQ1OT1基因的敲除降低了HSP90AA1的表达。KCNQ1OT1与HSP90AA1呈正相关,HSP90AA1从癌症基因组图谱数据库预测非小细胞肺癌的肿瘤进展。有趣的是,KCNQ1OT1通过海绵化miR-27b-3p来调节HSP90AA1的表达。MIR-27b-3p可拮抗KCNQ1OT1对HSP90AA1表达、H460细胞迁移和侵袭的影响。这些数据揭示了KCNQ1OT1作为癌基因通过miR-27b-3p/HSP90AA1轴在NSCLC进展过程中的作用。
Long noncoding RNA KCNQ1OT1 participates in the regulation of imprinted genes within the kcnq1 domain. But its roles in carcinogenesis and metastasis remain largely elusive. Herein, we evaluated its potential in non-small-cell lung cancer (NSCLC) progression. We demonstrated that the KCNQ1OT1 level was upregulated in NSCLC tissues and cell lines. High KCNQ1OT1 level correlated with poor overall and progression-free survival in NSCLC patients. KCNQ1OT1 facilitated proliferation, migration, and invasion in H460 cells. Furthermore, knockdown of KCNQ1OT1 reduced the expression of HSP90AA1. KCNQ1OT1 presented a positive correlation with HSP90AA1 which predicted the tumor progression in NSCLC from The Cancer Genome Atlas database. Intriguingly, KCNQ1OT1 modulated HSP90AA1 expression by sponging miR-27b-3p. MiR-27b-3p counteracted the effect of KCNQ1OT1 on HSP90AA1 expression, H460 cell migration, and invasion. These data revealed a role for KCNQ1OT1 as an oncogene through miR-27b-3p/HSP90AA1 axis during NSCLC progression.