miR-145 Inhibits Migration and Invasion of Glioma Stem Cells by Targeting ABCG2

Abstract

Despite advances in clinical therapies and technologies, the prognosis for patients with malignant glioma is poor. Our previous research demonstrated that glioma stem cells (GSCs) were crucial for glioma malignancy and accelerated tumor migration and invasion. The migration and invasion of malignant glioma cells into the surrounding normal brain tissues cause the poor outcome. miR-145, a miRNA found to be expressed in neurons, was recently found to have reduced expression in glioblastoma multiforme tumors. And miR-145 loss in glioma cells led to increased cell proliferation and invasion. However, its function on the migration and invasion of GSCs was still unknown. In this study, we aimed to identify the effects and mechanisms of miR-145 on the migration and invasion of GSCs. Our investigations revealed that miR-145 was low expressed in malignant glioma tissues and their corresponding GSCs. Knockdown of miR-145 in vitro could enhance the migration and invasion of GSCs, while up-regulation of miR-145 had the opposite effects. Further investigation of the potential mechanism demonstrated that the function of miR-145 in regulating the migration and invasion of GSCs is mediated by its targeting of ABCG2 mRNA. ABCG2 is an ATP-binding cassette transporter protein, which was identified to be overexpressed in GSCs and higher-grade glioma tissues. We found that miR-145 was negative correlated with ABCG2 levels in GSCs, and reduction in ABCG2 expression decreased the cell migration and invasion of GSCs. Further, a luciferase reporter proved that ABCG2 was a direct target of miR-145 in GSCs. Thus, these findings underscore the potential of miR-145 to regulate the migration and invasion of GSCs through targeting ABCG2.

MiR-454 Prompts Cell Proliferation of Human Colorectal Cancer Cells by Repressing CYLD Expression

“…It has been well established that microRNAs (miRNAs) are a large group of post-transcriptional gene regulators that potentially play essential roles in multiple biological processes, including cell differentiation, proliferation, angiogenesis, invasion and migration (Bartel, 2004;Esquela-Kerscher and Slack, 2006;Shi et al, 2014;Zhong et al, 2014). Recently, deregulation of miRNAs in cancer cells and their roles in tumorigenesis have been increasingly investigated (Calin and Croce, 2006;Esquela-Kerscher and Slack, 2006;Rico-Rosillo et al, 2014).…”

Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6

“…Many recent studies have revealed that miRNAs regulate the behavior of GSCs and may have similar functions to oncogenes or tumor suppressors [4]. For example, miR-20a and miR-106a enhance the invasiveness of GSCs [5], whereas miR-145 inhibits the migration and invasion of GSCs [6]. MiR-29a belongs to the miR-29 family, which consists of miR-29a, -29b and -29c.…”

Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug Sunitinib in Glioblastoma

“…Moreover, ADAM17, NEDD9, and ROCK1 have been identified as target genes by which miR-145 exerts antitumoral effect [19][20][21]. On the other hand, miR-145 appears to regulate OCT4, SOX2, and KLF4, the pluripotency factors of human stem cells, inhibited migration, invasion, and self-renewal of glioma stem cells [22][23][24]. Based on these reported activities of miR145, we hypothesized that miR-145 mimic might enhance the antitumoral activity of Sunitinib.…”