Cancer Biomark. 2019;26(1):63-68. doi: 10.3233/CBM-190289.
MicroRNAs (miRNAs; miR) have been proven to act as both oncogenes and tumor suppressors. However, the mechanism of action of miR429 in melanoma cells remains to be elusive. The present study aims to explain the functional role and mechanism of miR429 in the pathogenesis of melanoma. In our study, we have demonstrated that has-miRNA429 (miR429) is a tumor suppressor in melanoma cells. Luciferase reporter assays demonstrated that the overexpression of miR429 reduced the transcriptional activity of AKT serine/threonine kinase 1 (AKT1). Furthermore, the results showed that the mRNA and protein expression levels of AKT1 were downregulated in the melanoma cell lines when miR429 was overexpressed according to qRT-PCR and western bolt, indicating MicroRNA-429 may directly target AKT1 in melanoma. In vivo, overexpression miR-429 could obviously enhance the inhibition effect of tumor size and weight in the nude mice. Taken together, our findings suggest that novel miR429-regulated pathway may serve as new insights into melanoma oncogenesis and metastasis.
MicroRNAs (miRNAs; miR) 已被证明既能作为癌基因,也能作为肿瘤抑制因子发挥作用。然而,miR429 在黑色素瘤细胞中的作用机制仍难以捉摸。本研究旨在解释 miR429 在黑色素瘤发病机制中的功能作用和机制。在我们的研究中,我们已经证明了 has-miRNA429 (miR429) 是黑色素瘤细胞中的肿瘤抑制因子。荧光素酶报告基因检测表明,miR429 的过表达降低了 AKT 丝氨酸/苏氨酸激酶 1 (AKT1) 的转录活性。此外,根据 qRT-PCR 和 western blot 结果显示,当 miR429 过表达时,黑色素瘤细胞系中 AKT1 的 mRNA 和蛋白表达水平下调,表明 MicroRNA-429 可能直接靶向黑色素瘤中的 AKT1。在体内,过表达 miR-429 可明显增强裸鼠肿瘤大小和重量的抑制作用。综上所述,我们的研究结果表明,新型 miR429 调控途径可能为黑色素瘤的发生和转移提供新的见解。