Ionizing Radiation-inducible microRNA-21 Induces Angiogenesis by Directly Targeting PTEN

Yongchun Zhang,Zhiying Chen,Peng Jiang,Lingxin Feng,Xiang Wang,Xiumei Li

doi:10.31557/apjcp.2019.20.5.1587

Abstract

Background:Previous experimental studies have established that MicroRNAs (miRNAs) can function as oncogenes or tumor suppressors in the regulation of tumor biology or pathology. However, the effects of ionizing radiation (IR) on the expression levels of cellular miRNAs and their further effects on the biological behavior of tumor cells require further investigation.Methods:We determined the proliferation, migration and tube formation of HUVEC cells after ionizing radiation (control, 0h and 24h), and the changes of miR-21, VEFG and HIF-1α levels after ionizing radiation were measured by Western blot (WB). The effects of miR-21 mimics and inhibitors on the protein and mRNA expression of PTEN were determined by RT-PCT and WB. Two independent luciferase reporter plasmids were constructed to detect changes in PTEN protein expression.Results:We found that both IR and miR-21 increase proliferation, migration and tube formation of HUVEC cells. Ionizing radiation directly targets the inhibition of PTEN expression by causing an increase in miR-21 expression, and induces the accumulation of VEGF and HIF-1α expression in cells by the PI3K / AKT signaling pathway. Simultaneous induction of ectopic expression of PTEN can rescue radiation-induced proliferation, migration and tube formation in tumor cells.Conclusion:miR-21 promotes tumor cell proliferation and migration by targeting inhibition of PTEN expression, which may become a potential target for tumor therapy in the future.

Highlights

Ionizing radiation, as a high-energy physics damaging factors, can produce free radicals by ionizing stimulation, resulting in the alteration of a number of ionizing radiation inducible genes (IRIG)
Expressed micro RNA (miRNA) are detected in many cancer types and play critical roles in tumor biology, such as cell apoptosis and metastasis (Lu et al, 2005; Esquela-Kerscher and Slack, 2006; Hwang and Mendell, 2007; Landgraf et al, 2007)
Little is known about the functional role of miRNAs in participating the angiogenesis, which is a critical process in cancer development (Soucek et al, 2007), stimulating by hypoxia, cytokines, and growth factors (Semenza,2001, Goh et al, 2007; Liao and Johnson, 2007)

Summary

Introduction

As a high-energy physics damaging factors, can produce free radicals by ionizing stimulation, resulting in the alteration of a number of ionizing radiation inducible genes (IRIG). We demonstrated of miR-21 overexpression induced by ionization, which could increased HIF-1a and VEGF expression by PI3K/AKT/PTEN signaling pathway and induced tumor angiogenesis. Methods: We determined the proliferation, migration and tube formation of HUVEC cells after ionizing radiation (control, 0h and 24h), and the changes of miR-21, VEFG and HIF-1α levels after ionizing radiation were measured by Western blot (WB). Results: We found that both IR and miR-21 increase proliferation, migration and tube formation of HUVEC cells. Ionizing radiation directly targets the inhibition of PTEN expression by causing an increase in miR-21 expression, and induces the accumulation of VEGF and HIF-1α expression in cells by the PI3K / AKT signaling pathway. Simultaneous induction of ectopic expression of PTEN can rescue radiation-induced proliferation, migration and tube formation in tumor cells. Conclusion: miR-21 promotes tumor cell proliferation and migration by targeting inhibition of PTEN expression, which may become a potential target for tumor therapy in the future

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