Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
FEBS Lett. 2012 May 7;586(9):1312-7. doi: 10.1016/j.febslet.2012.03.035. Epub 2012 Mar 27.
MicroRNAs (miRNAs) exhibit tumor-specific expression signatures and play crucial roles in tumorigenesis by targeting oncogenes. Here, through analyzing the miRNA-array profiles of human glioblastoma tissues and the adjacent normal brain tissues, we found miR-483-5p was significantly down-regulated in gliomas, which was confirmed in both human glioma specimens and cell lines. The overexpression of miR-483-5p suppressed glioma cell proliferation and induced a G0/G1 arrest. In contrast, miR-483-5p inhibition promoted cell proliferation. Furthermore, by a dual-luciferase reporter assay and expression analysis, we identified extracellular signal-regulated kinase 1 (ERK1) as a direct target of miR-483-5p. ERK1 knockdown can block cell proliferation induced by miR-483-5p inhibition. Thus, our findings provide the first evidence that miR-483-5p can serve as a tumor suppressor in gliomas.
微小 RNA（miRNAs）表现出肿瘤特异性表达特征，并通过靶向癌基因在肿瘤发生中发挥关键作用。在这里，通过分析人胶质母细胞瘤组织和相邻正常脑组织的 miRNA 芯片图谱，我们发现 miR-483-5p 在神经胶质瘤中显著下调，这在人类神经胶质瘤标本和细胞系中均得到了证实。miR-483-5p 的过表达抑制了神经胶质瘤细胞的增殖，并诱导 G0/G1 期停滞。相反，miR-483-5p 的抑制促进了细胞增殖。此外，通过双荧光素酶报告基因检测和表达分析，我们确定细胞外信号调节激酶 1（ERK1）是 miR-483-5p 的直接靶标。ERK1 的敲低可以阻断 miR-483-5p 抑制引起的细胞增殖。因此，我们的研究结果首次提供了证据，表明 miR-483-5p 可以作为神经胶质瘤中的肿瘤抑制因子。
