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TGF-β 诱导的 miR10a/b 表达通过靶向 PTEN 促进人神经胶质瘤细胞迁移。

TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215004, P.R. China.

出版信息

Mol Med Rep. 2013 Dec;8(6):1741-6. doi: 10.3892/mmr.2013.1709. Epub 2013 Oct 1.

Abstract

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.

摘要

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。

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