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微小RNA-181a-5p通过靶向血管细胞黏附分子-1抑制白细胞介素-17诱导的非小细胞肺癌增殖和迁移。

MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1.

作者信息

Cao Yang, Zhao Dan, Li Ping, Wang Lanrong, Qiao Bingli, Qin Xiaoyan, Li Lei, Wang Yang

机构信息

Department of Oncology, The Third People's Hospital of Zhengzhou, Zhengzhou, China.

Department of Obstetrical, Women and Infants Hospital of Zhengzhou, Zhengzhou, China.

出版信息

Cell Physiol Biochem. 2017;42(1):346-356. doi: 10.1159/000477389. Epub 2017 May 25.

Abstract

AIM

The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC.

METHODS

35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL) of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1) expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration.

RESULTS

miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3'-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3.

CONCLUSION

Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.

摘要

目的

文献报道了炎症介质白细胞介素-17(IL-17)在非小细胞肺癌(NSCLC)恶性肿瘤中的作用。微小RNA-181a-5p(miR-181a-5p)作为一种肿瘤抑制因子,可在转录后水平调控靶基因。本研究旨在探讨NSCLC中IL-17与miR-181a-5p之间的相互作用。

方法

本研究选取了35例NSCLC患者和24例慢性阻塞性肺疾病(COPD)对照者进行检测。在体外,将H226和H460细胞系暴露于不同剂量(20、40、60和80 ng/mL)的IL-17中,以检测IL-17对miR-181a-5p和血管细胞黏附分子1(VCAM-1)表达的影响。转染miR-181模拟物和miR-181a-5p抑制剂,以探究其对VCAM-1以及肿瘤细胞增殖和迁移的调控作用。

结果

NSCLC组织中miR-181a-5p表达下调,IL-17和VCAM-1表达上调。此外,IL-17降低了H226和H460细胞中miR-181a-5p的表达,但增加了VCAM-1的表达。miR-181通过与3'-UTR序列结合来调控VCAM-1的表达。miR-181减弱了肿瘤细胞的增殖和迁移。IL-17通过激活NF-κB而非Stat3来调节miR-181a-5p的表达。

结论

综上所述,我们的数据表明在IL-17暴露下miR-181a-5p对VCAM-1表达具有调控作用,这为对抗癌症转移提供了一种潜在途径。

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