The Fourth Clinical Hospital of Minimally Invasive Neurosurgery, Harbin Medical University, Harbin 150001, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Jan;46(1):48-55. doi: 10.1093/abbs/gmt124. Epub 2013 Dec 16.
MicroRNAs (miRNAs) function as key regulators of gene expression in various cancers. In this study, the aim is to explore the roles and regulation mechanism of miR-181c in neuroblastoma (NB) cells. We found that miR-181c was downregulated in metastatic NB tissues, compared with primary NB tissues. Then functional studies indicated that miR-181c overexpression inhibited NB cell proliferation, migration, and invasion, while miR-181c inhibition increased cell proliferation, migration, and invasion. EGFP reporter assay, real-time polymerase chain reaction and western blot analysis validated that Smad7 was a direct target of miR-181c. MiR-181c reduced Smad7 expression at both mRNA and protein levels. Finally, functional assays showed that the effect of Smad7 knockdown on cells was similar to that of miR-181c overexpression. Importantly, Smad7 overexpression could restore the antitumor effects that were induced by miR-181c. In conclusion, our results demonstrated that miR-181c inhibits NB cell growth and metastasis-related traits through the suppression of Smad7, functioning as a tumor suppressor. Moreover, our results suggested that miR-181c may serve as an important therapeutic target for NB patients.
微小 RNA(miRNAs)在各种癌症中作为基因表达的关键调节剂发挥作用。在这项研究中,旨在探索 miR-181c 在神经母细胞瘤(NB)细胞中的作用和调节机制。我们发现,与原发性 NB 组织相比,转移性 NB 组织中 miR-181c 下调。然后功能研究表明,miR-181c 过表达抑制 NB 细胞增殖、迁移和侵袭,而 miR-181c 抑制则增加细胞增殖、迁移和侵袭。EGFP 报告基因检测、实时聚合酶链反应和 Western blot 分析验证 Smad7 是 miR-181c 的直接靶标。miR-181c 在 mRNA 和蛋白水平上降低 Smad7 的表达。最后,功能测定表明 Smad7 敲低对细胞的作用与 miR-181c 过表达相似。重要的是,Smad7 过表达可以恢复 miR-181c 诱导的抗肿瘤作用。总之,我们的结果表明,miR-181c 通过抑制 Smad7 抑制 NB 细胞的生长和转移相关特征,发挥肿瘤抑制作用。此外,我们的结果表明,miR-181c 可能是 NB 患者的一个重要治疗靶点。