Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Eur J Cancer. 2012 Nov;48(16):3104-11. doi: 10.1016/j.ejca.2012.02.007. Epub 2012 Mar 7.
MicroRNAs are strongly implicated in cancer but their specific roles and functions in the major cancers have yet to be fully elucidated. In this study, we defined the expression and function of miR-137, which we found to be downregulated in glioma samples and glioma cells by qRT-PCR. Ectopic expression of miR-137 in glioma cell lines inhibited proliferation and invasion. Using computational and expression analysis, Cox-2 was identified as a candidate target of miR-137. Reporter assay with 3'UTR of Cox-2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-137, providing strong evidence that miR-137 was a direct regulator of Cox-2. Expression analysis further revealed that Cox-2 was elevated in glioma and associated with survival of patients. Furthermore, we observed that Cox-2 knockdown resulted in effects similar to those with miR-137 transfection in glioma cells. In conclusion, our study demonstrates that miR-137 deregulation is common in glioma, and restoration of its function inhibits cell proliferation and invasion, suggesting that miR-137 may act as a tumour suppressor.
MicroRNAs 在癌症中起重要作用,但它们在主要癌症中的具体作用和功能尚未完全阐明。在本研究中,我们通过 qRT-PCR 确定了 miR-137 在神经胶质瘤样本和神经胶质瘤细胞中的表达和功能,发现其表达下调。miR-137 在神经胶质瘤细胞系中的异位表达抑制了增殖和侵袭。通过计算和表达分析,鉴定出 Cox-2 是 miR-137 的候选靶标。将 Cox-2 的 3'UTR 克隆到下游的荧光素酶基因的报告基因实验显示,在存在 miR-137 的情况下,荧光素酶活性降低,这为 miR-137 是 Cox-2 的直接调节因子提供了有力证据。表达分析进一步表明,Cox-2 在神经胶质瘤中上调,并与患者的生存相关。此外,我们观察到 Cox-2 的敲低导致与 miR-137 转染在神经胶质瘤细胞中的效果相似。总之,我们的研究表明,miR-137 在神经胶质瘤中失调常见,恢复其功能抑制细胞增殖和侵袭,表明 miR-137 可能作为肿瘤抑制因子发挥作用。