Department of Neurosurgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215004, P.R. China.
Mol Med Rep. 2013 Dec;8(6):1741-6. doi: 10.3892/mmr.2013.1709. Epub 2013 Oct 1.
Human gliomas are associated with high rates of morbidity and mortality. In the brain, increased mRNA levels of transforming growth factor β (TGF-β) correlate with the degree of malignancy of human gliomas. miR10a/10b expression has been demonstrated to be associated with TGF-β expression in brain tumors, and it is reported that TGF-β induces miR10 expression. Therefore, miR10a/10b expression may be induced by TGF-β expression and may be involved in the TGF-β-induced migration of brain tumor cells. The present study examined the expression of TGF-β and miR10a/10b in the tissues of 10 patients with brain tumors using quantitative PCR (qPCR), and the correlation between TGF-β and miR10a or miR10b expression was analyzed. Additionally, U251 and SHG-44 cells were treated with TGF-β and the expression of miR10a/10b was examined. Further, cell migration was analyzed following transfection of U251 cells with miR10a/10b and the association between miR10a/10b and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was investigated. U251 cells were transfected with miR10a/10b inhibitors and a PTEN expression plasmid prior to TGF-β treatment and then cell migration was assessed. A significant correlation was identified between TGF-β and miR10a expression (r2=0.6936, P=0.007) and between TGF-β and miR10b expression (r2=0.5876, P=0.02) in the tissues of patients with brain tumors. The results also showed that TGF-β induces miR10a/10b expression and that TGF-β-induced miR10a/10b expression promotes cell migration through the suppression of PTEN. In conclusion, TGF-β-induced miR10a/10b promotes brain tumor migration. This study may provide a number of suggestions for the clinical treatment of brain tumors.
人类脑胶质瘤与高发病率和死亡率相关。在大脑中，转化生长因子β（TGF-β）的 mRNA 水平升高与人类脑胶质瘤的恶性程度相关。已经证明 miR10a/10b 的表达与脑肿瘤中的 TGF-β表达相关，并且据报道 TGF-β诱导 miR10 的表达。因此，miR10a/10b 的表达可能是由 TGF-β表达诱导的，并且可能参与 TGF-β诱导的脑肿瘤细胞迁移。本研究使用定量 PCR（qPCR）检查了 10 例脑肿瘤患者组织中 TGF-β和 miR10a/10b 的表达，并分析了 TGF-β与 miR10a 或 miR10b 表达之间的相关性。此外，用 TGF-β处理 U251 和 SHG-44 细胞，并检查 miR10a/10b 的表达。进一步，在用 miR10a/10b 转染 U251 细胞后分析细胞迁移，并研究 miR10a/10b 与染色体 10 上缺失的磷酸酶和张力蛋白同源物（PTEN）之间的关系。在用 TGF-β处理之前，用 miR10a/10b 抑制剂和 PTEN 表达质粒转染 U251 细胞，然后评估细胞迁移。在脑肿瘤患者的组织中，鉴定出 TGF-β与 miR10a 表达之间（r2=0.6936，P=0.007）和 TGF-β与 miR10b 表达之间（r2=0.5876，P=0.02）存在显著相关性。结果还表明，TGF-β诱导 miR10a/10b 的表达，并且 TGF-β诱导的 miR10a/10b 表达通过抑制 PTEN 促进细胞迁移。总之，TGF-β诱导的 miR10a/10b 促进脑肿瘤迁移。本研究可能为脑肿瘤的临床治疗提供一些建议。
