Overexpression of miR-145 in U87 cells reduces glioma cell malignant phenotype and promotes survival after in vivo implantation

Abstract

In the present study, we sought to elucidate the effect of miR-145 on glioma cell progression and its mechanisms of action. We examined the effects of miR-145 on proliferation and invasion of U87 glioma cells and on capillary tube formation. Our data show that restoration of miR-145 in U87 glioma cells significantly reduced their in vitro proliferation, invasion and angiogenesis. However, decreased miR-145 expression promoted U87 glioma cell proliferation, invasion and angiogenesis, and reduced-expression of miR-145 increased ADAM17 and EGFR expression in U87 cells. Overexpression of miR-145 reduced ADAM17 and EGFR expression. VEGF secretion and VEGF expression were decreased by increased miR-145 expression in U87 cells and were reversed by miR-145 down-regulation in vitro. Nude mice with intracerebral implantation of U87 overexpressing miR-145 cells exhibited significantly reduced tumor growth and promoted survival compared with control groups. Taken together, these results suggest a role for miR-145 as a tumor suppressor which inhibits glioma cell proliferation, invasion and angiogenesis in vitro and reduces glioma growth in vivo.

MiR-23a transcriptional activated by Runx2 increases metastatic potential of mouse hepatoma cell via directly targeting Mgat3

“…Our miRNA microarray analyses showed that miR-23a expression levels were significantly higher in Hca-P cells (with lymphatic metastatic potential) than in Hepa1–6 cells (with no lymphatic metastatic potential) 27 , while the relative expressions of miR-23a were higher than several tumor malignancy related miRNAs 9 , 10 , 16 , 20 , 21 , 28 , 29 in the two mouse HCC cell lines (Fig. 1a ).…”

“…( a ) miRNA microarray was performed to compare the miRNA expression profiles of Hca-P and Hepa1–6 cells (left) 27 . The relative expression of miR-23a and several miRNAs, which are related to tumor malignancy 9 , 10 , 16 , 20 , 21 , 28 , 29 , measured by microarray is displayed as a histogram (right). ( b ) The relative expression of miR-23a in Hca-P and Hepa1–6 cells as measured by qRT-PCR.…”

Molecular and Genetic Determinants of Glioma Cell Invasion

“…About 50% of EGFR -amplified GBM express a ligand-independent truncated mutant variant, EGFRvIII, which is characterized by genomic deletion of exons 2–7, resulting in a constitutively active oncogenic form [ 47 ]. The presence of EGFR mutations significantly promotes the invasive capacity of glioma cells through the regulation of integrin [ 48 , 49 ], CAMs [ 50 ], urokinase-type plasminogen activator/receptor (uPA/uPAR) [ 51 , 52 ], MMPs [ 53 , 54 ] and microRNAs [ 55 , 56 ]. Wild-type EGFR is reported to be involved in the switch between invasive and angiogenic phenotypes in GBM [ 57 ].…”

Transfer of functional microRNAs between glioblastoma and microvascular endothelial cells through gap junctions

“…We used the U87 human glioblastoma cell line and HMEC, and focused on two human mature miRs, namely miR-145-5p which is expressed in HMEC but not in U87 [17], and miR-5096 which is expressed in U87 [4] but not reported in HMEC. We demonstrate an exchange of these two miRs between the two cell types through the same gap junction pathway.…”

“…A miR is single-stranded and ~21nucleotides long, forming a linear molecule with a diameter of ~1.0 nm, which is in the same order of the gap junction channel pore size [ 15 , 16 ]. We have recently reported that miR-145-5p, which reduces glioma growth [ 17 ], could be exchanged between HMEC and colon cancer cells through gap junctions formed by Cx43 [ 18 ].…”