Li Ying-Jie, Ping Chen, Tang Jian, Zhang Wen
Department of Cardio-Thoracic Surgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, 100048, China.
Cell Biol Int. 2016 Jun;40(6):621-8. doi: 10.1002/cbin.10584. Epub 2016 Mar 23.
MicroRNA-455 (miRNA-455), which is downregulated in human cancer, potently mediates the multiple steps of carcinogenesis. However, the role of miR-455 in non-small cell lung cancer (NSCLC) carcinogenesis remains unclear. In present study, we determined the mature miRNA-455 expression in NSCLC tissues and cells by real-time PCR. Follow-up studies examined the effects of a miR-455 mimic (gain of function) on cell proliferation, migration, and invasion. Our data indicate that miR-455 was significantly down-regulated in NSCLC cell lines and tissues. In functional assays, overexpression of miR-455 suppressed the proliferation, migration, and invasion of NSCLC cell lines. Data from reporter assays showed that miR-455 directly binds to 3'UTR of ZEB1 and suppresses the endogenous level of ZEB1 protein expression. Furthermore, overexpression of ZEB1 reverses miR-455-suppressed malignant phenotype of NSCLC cells. Moreover, we found that upregulation of ZEB1 expression is inversely associated with miR-455 expression in NSCLC tissues. Taken together, miR-455 as an anti-oncogene in non-small cell lung cancer through up-regulation of ZEB1 and serve as a potential therapeutic target in NSCLC.
微小RNA-455（miRNA-455）在人类癌症中表达下调，有力地介导了癌症发生的多个步骤。然而，miR-455在非小细胞肺癌（NSCLC）发生中的作用仍不清楚。在本研究中，我们通过实时PCR测定了NSCLC组织和细胞中成熟miRNA-455的表达。后续研究检测了miR-455模拟物（功能获得）对细胞增殖、迁移和侵袭的影响。我们的数据表明，miR-455在NSCLC细胞系和组织中显著下调。在功能试验中，miR-455的过表达抑制了NSCLC细胞系的增殖、迁移和侵袭。报告基因试验数据表明，miR-455直接结合ZEB1的3'UTR并抑制ZEB1蛋白表达的内源性水平。此外，ZEB1的过表达逆转了miR-455抑制的NSCLC细胞的恶性表型。此外，我们发现NSCLC组织中ZEB1表达的上调与miR-455表达呈负相关。综上所述，miR-455作为非小细胞肺癌中的一种抑癌基因，通过上调ZEB1发挥作用，并可作为NSCLC的潜在治疗靶点。
