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

Abstract

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.

Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment

“…TGF- β induces the expression of miR-10a/10b in the tissues of brain tumour patients [36]. All three miRNAs of miR-23a~27a~24-2 cluster are among the identified miRNAs panel of this study.…”

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

“…4B and 4E ). In addition, two recent studies reported that miR-10b directly targets PTEN (21, 39). Indeed, compared with MMTV-PyMT;miR-10b +/+ mice, MMTV-PyMT;miR-10b −/− mice displayed upregulation of Pten and downregulation of phospho-Akt in both primary mammary tumors (Fig.…”

“…When overexpressed, miR-10b can induce motility and invasiveness of various cancer cell lines (5, 15, 16, 18-21) and promote metastasis in xenograft models (5, 15, 20) through direct targeting of HOXD10 , NF1 , KLF4 , PTEN , and likely other genes. Conversely, silencing miR-10b expression suppresses cancer cell proliferation, migration, and invasion in vitro as well as tumor growth or metastasis in vivo (14, 18, 19, 22), suggesting that miR-10b is a potential target for anti-tumor or anti-metastatic therapy.…”

Molecular Mechanisms of Glioma Cell Motility

“…Other mechanisms of TGF-β influencing the ECM and promoting migration include the upregulation of integrin avβ3 and the versican isoforms V0/V1 (84,153). Furthermore, TGF-β suppresses phosphatase and tensin homolog (PTEN) in glioma cells through enhanced miR10a/b expression (154). In patient samples, TGFB1I1 (TGF-β1-induced transcript 1) expression was found to be correlated with tumor grade, and activation of EMT pathways (152).…”