School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
Biomed Pharmacother. 2017 Dec;96:596-602. doi: 10.1016/j.biopha.2017.10.031. Epub 2017 Oct 13.
As the most common primary central nervous system tumor, glioma is characterized by high levels of mortality and migration. Unclear boundary with normal brain tissue results in poor treatment. The mammalian diaphanous-related formin 1 (Diaph1) which belongs to formin-homology protein family, is a target of RhoA and involved in a number of actin-related biological processes, which abnormally expressed in pathological conditions in a number of tumors. Immunohistochemical analysis showed that Diaph1 was overexpressed in glioma tissues compared with normal human brain tissue. Diaph1 gene silencing RNA interference (RNAi) significantly inhibited the migratory activity of human glioma cell lines U87 and U251. Moreover, data obtained from qRT-PCR and Western-blot analysis showed that the mRNA and protein expression of matrix metalloproteinase2 and 9 (MMP2 and MMP9) was significantly suppressed in these Diaph1 knockdown cell lines, as well as gelatin zymography analysis revealed that the activity of MMP2 and MMP9 in conditioned medium was markedly decreased. In conclusion, our data demonstrate that Diaph1 is highly expressed in human glioma, plays a significant role in glioma cell migration, and can influence the expression and activity of MMP2 and MMP9 indirectly in human glioma cell lines U87 and U251. We provide a theoretical basis for further experimental studies and Diaph1 using on glioma therapy.
作为最常见的原发性中枢神经系统肿瘤，神经胶质瘤的特点是死亡率和迁移率高。与正常脑组织的界限不清导致治疗效果不佳。哺乳动物丝氨酸苏氨酸蛋白激酶相关形态发生因子 1（Diaph1）属于形态发生同源蛋白家族，是 RhoA 的靶标，参与许多与肌动蛋白相关的生物学过程，在许多肿瘤的病理条件下异常表达。免疫组织化学分析显示，Diaph1 在神经胶质瘤组织中的表达高于正常人脑组织。Diaph1 基因沉默 RNA 干扰（RNAi）显著抑制了人神经胶质瘤细胞系 U87 和 U251 的迁移活性。此外，qRT-PCR 和 Western-blot 分析数据显示，这些 Diaph1 敲低细胞系中基质金属蛋白酶 2 和 9（MMP2 和 MMP9）的 mRNA 和蛋白表达明显受到抑制，并且明胶酶谱分析显示条件培养基中 MMP2 和 MMP9 的活性明显降低。总之，我们的数据表明 Diaph1 在人神经胶质瘤中高度表达，在神经胶质瘤细胞迁移中起重要作用，并可间接影响 U87 和 U251 人神经胶质瘤细胞系中 MMP2 和 MMP9 的表达和活性。为进一步的实验研究和 Diaph1 在神经胶质瘤治疗中的应用提供了理论依据。
