miR-138-5p靶向Nir1调控胶质瘤细胞的侵袭

    miR-138-5p Promotes Glioma Cells Invasion by Targeting Nir1

    • 摘要:
      目的 探讨miR-138-5p与PYK2 N端结构域相互作用受体1(PYK2 N-terminal domain-interacting receptor 1,Nir1)之间的关系并判断其是否通过与Nir1结合影响胶质瘤的侵袭。
      方法 比较不同胶质瘤细胞系中miR-138-5p表达水平及其对胶质瘤细胞U251和H4中Nir1蛋白的影响、转染后胶质瘤细胞侵袭能力,检测miR-138-5p能否与Nir1靶向结合。
      结果 低侵袭人胶质瘤H4细胞中miR-138-5p的水平显著高于高侵袭性的胶质瘤U251、LN229和U87细胞(P<0.05);在U251、H4细胞中,miR-138-5p过表达组Nir1蛋白表达量较其对照组(miR-negative control,miR-NC)降低;miR-138-5p抑制组中Nir1蛋白表达量较其对照组(inhibitor NC)升高。然而,miR-138-5p过表达组中Nir1的mRNA水平较其对照组无明显改变(P>0.05)。miR-138-5p过表达组穿过基底膜小孔的U251、H4细胞数明显少于其对照组(P<0.05)。miR-138-5p过表达显著降低Nir1-3'-UTR的荧光素酶活性。
      结论 胶质瘤细胞中miR-138-5p与Nir1结合,可通过降低Nir1的翻译、减少Nir1蛋白的表达抑制胶质瘤细胞的侵袭能力。

       

      Abstract:
      Objective To investigate the relationship between miR-138-5p and PYK2 N-terminal domain-interacting receptor 1(Nir1)and determine whether miR-138-5p affects glioma invasion through binding with Nir1.
      Methods The expression level of miR-138-5p in different glioma cell lines and its effect on Nir1 protein in glioma cells U251 and H4 were compared, as well as the invasion ability of glioma cells after transfection, to detect whether miR-138-5p could target Nir1.
      Results The level of miR-138-5p in low-invasive human glioma H4 cells was significantly higher than that in highly invasive human glioma U251, LN229 and U87 cells(P < 0.05). In the U251 and H4 cell, the expression of Nir1 protein in the miR-138-5p overexpression groups was lower than that in the miR-negative control(miR-NC)group; the expression of Nir1 protein in miR-138-5p inhibitor group was increased in comparison with inhibitor NC group. However, Nir1 mRNA level in miR-138-5p overexpression group had no significant changes compared with the miR-NC group(P>0.05). The number of U251 and H4 cells in the miR-138-5p overexpression group passing through the small hole in the basement membrane was significantly less than that in the miR-NC group(P < 0.05). miR-138-5p overexpression significantly reduced luciferase activity of Nir1-3'-UTR.
      Conclusions miR-138-5p binding to Nir1 in glioma cells, which can inhibit the invasion of glioma cells by reducing the translation of Nir1 and the expression of Nir1 protein.

       

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