微小RNA-204通过靶向JAK2抑制非小细胞肺癌（NSCLC）的侵袭和迁移。

miR-204 suppresses non-small-cell lung carcinoma (NSCLC) invasion and migration by targeting JAK2.

作者信息

Wang P, Lv H Y, Zhou D M, Zhang E N

机构信息

Department of Oncology, the Yantaishan Hospital, Yantai, Shandong Province, China.

Department of Oncology, The Qingdao School of Medicine, Yantai, Shandong Province, China.

出版信息

Genet Mol Res. 2016 May 20;15(2):gmr6415. doi: 10.4238/gmr.15026415.

DOI:10.4238/gmr.15026415

PMID:27323056

Abstract

Aberrant expression of microRNA is associated with the development and progression of cancers. MicroRNA-204 (miR-204) down-regulation has been previously demonstrated in non-small-cell lung carcinoma (NSCLC); however, the underlying mechanism by which miR-204 suppresses tumorigenesis in NSCLC remains elusive. In this study, miR-204 expression was found to be down-regulated, and that of Janus kinase 2 (JAK2) was found to be up-regulated in four NSCLC cell lines (A549, H1299, H1650, and H358) compared to the normal lung cell line. The overexpression of miR-204 suppressed the invasive and migratory capacities of H1299 cells. A luciferase assay confirmed that the binding of miR-124 to the -untranslated region of JAK2 inhibited the expression of JAK2 proteins in H1299 cells. JAK-2 overexpression effectively reversed miR-204-repressed NSCLC metastasis. Taken together, our findings revealed that miR-204 functions as a tumor suppressor in NSCLC by targeting JAK2, and that miR-204 may therefore serve as a biomarker for the diagnosis and treatment of NSCLC.

摘要

微小RNA的异常表达与癌症的发生和发展相关。先前已证实在非小细胞肺癌（NSCLC）中微小RNA-204（miR-204）表达下调；然而，miR-204抑制NSCLC肿瘤发生的潜在机制仍不清楚。在本研究中，与正常肺细胞系相比，发现四种NSCLC细胞系（A549、H1299、H1650和H358）中miR-204表达下调，而Janus激酶2（JAK2）表达上调。miR-204的过表达抑制了H1299细胞的侵袭和迁移能力。荧光素酶报告基因检测证实，miR-124与JAK2的非翻译区结合可抑制H1299细胞中JAK2蛋白的表达。JAK-2过表达有效逆转了miR-204抑制的NSCLC转移。综上所述，我们的研究结果表明，miR-204通过靶向JAK2在NSCLC中发挥肿瘤抑制作用，因此miR-204可能作为NSCLC诊断和治疗的生物标志物。