MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2
MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2
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DOI：
10.1016/j.gene.2018.03.020
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发表时间：
2018-06-05
期刊：
影响因子：
3.5
通讯作者：
Wu, Zhangyi
中科院分区：
文献类型：
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作者：
Lin, Yihai;Wu, Zhangyi
MicroRNA（miRNA）是一类小的非编码RNA，通过靶向3 '-非翻译区（3'-UTR）调控信使RNA（mRNA），从而抑制基因表达。本研究通过真实的时间PCR检测了miR-128在胶质瘤组织和胶质瘤细胞中的表达和功能。miR-128模拟物在LN 229和U251细胞中过表达可抑制胶质瘤细胞的增殖和侵袭。然而，miR-128模拟物对胶质瘤细胞侵袭和增殖的抑制作用可被过表达的环氧化酶-2（考克斯-2）逆转。我们的数据显示考克斯-2是miR-128的候选靶点。在miR-128的存在下，考克斯-2的3 '-UTR的荧光素酶活性降低。另外，通过真实的时间PCR检测，miR-128明显降低了考克斯-2 mRNA的稳定性。结果发现，miR-128抑制剂可显著增加胶质瘤细胞考克斯-2 mRNA的表达，并上调MMP 9和ki 67蛋白的表达，促进胶质瘤细胞的增殖。此外，3 '-UTR的荧光素酶活性被miR-128抑制剂上调。所有这些结果支持miR-128是考克斯-2的直接调节剂。进一步的研究表明，考克斯-2在胶质瘤组织中表达升高，其表达与miR-128水平呈负相关。这些发现可能使miR-128成为治疗胶质瘤患者的新的潜在靶点。
MicroRNAs (miRNA), a class of small noncoding RNAs, regulates message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) resulting in suppression of gene expression. In this study, we identified the expression and function of miR-128, which was found to be downregulated in glioma tissues and glioma cells by real time PCR. Overexpression of miR-128 mimics into LN229 and U251 cells could inhibit proliferation and invasion of glioma cells. However, the inhibitory effects of miR-128 mimics on the invasion and proliferation of glioma cells were reversed by overexpression of cyclooxygenase-2 (COX-2). Our data showed that COX-2 was a candidate target of miR-128. Luciferase activity of 3'-UTR of COX-2 was reduced in the presence of miR-128. Additionally, miR-128 obviously decreased COX-2 mRNA stability determined by real time PCR. Contrarily, we found that miR-128 inhibitor significantly increased the COX-2 mRNA expression, and elevated the protein expression of MMP9 and ki67, and promoted the proliferation of glioma cells. Furthermore, luciferase activity of the 3'-UTR was upregulated by miR-128 inhibitor. All of these results supported that miR-128 was a direct regulator of COX-2. Further studies proved that COX-2 was elevated in glioma tissues and its expression was negatively correlated with the levels of miR-128. These findings may establish miR-128 as a new potential target for the treatment of patients with gliomas.