Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Brain Res. 2011 May 10;1389:9-18. doi: 10.1016/j.brainres.2011.03.013. Epub 2011 Mar 16.
MicroRNAs are small endogenous noncoding RNAs, which modulate target gene expression by binding with target mRNA sequences in the 3'untranslated region (UTR) with an imperfect complementarity that inhibits the mRNA translation. Many microRNAs have been reported to function as tumor oncogenes or anti-oncogenes. Recently, more and more microRNAs have been reported to contribute to a tumor's invasive potential. Here, we show that microRNA-10b (miR-10b) was over-expressed in glioma samples and directly associated with the glioma's pathological grade and malignancy. We also found that miR-10b induced glioma cell invasion by modulating tumor invasion factors MMP-14 and uPAR expression via the direct target HOXD10. The miR-10b/HOXD10/MMP-14/uPAR signaling pathway might contribute to the invasion of glioma. Accordingly, glioma cells lost their invasive ability when treated with specific antisense oligonucleotides (miR-10b inhibitors), suggesting that miR-10b could be used as a new bio-target to cure glioma.
微 RNA 是小型内源性非编码 RNA,通过与 3'非翻译区 (UTR) 中的靶 mRNA 序列结合以不完全互补的方式调节靶基因表达,从而抑制 mRNA 翻译。许多 microRNAs 被报道具有肿瘤癌基因或抑癌基因的功能。最近,越来越多的 microRNAs 被报道有助于肿瘤的侵袭潜能。在这里,我们显示 microRNA-10b (miR-10b) 在神经胶质瘤样本中过表达,并且直接与神经胶质瘤的病理分级和恶性程度相关。我们还发现 miR-10b 通过直接靶向 HOXD10 调节肿瘤侵袭因子 MMP-14 和 uPAR 的表达来诱导神经胶质瘤细胞侵袭。miR-10b/HOXD10/MMP-14/uPAR 信号通路可能有助于神经胶质瘤的侵袭。相应地,当用特异性反义寡核苷酸 (miR-10b 抑制剂) 处理神经胶质瘤细胞时,它们失去了侵袭能力,这表明 miR-10b 可用作治疗神经胶质瘤的新生物靶标。