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

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.

The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS

“…MiR-221-5p inhibition restored the expression of EPAS1 but not EFNB2, and miR-21a-3p inhibition restored the expression of E2F8 but not EPAS1. MiR-21 had been reported to increase proliferation, migration and tube formation of Human Umbilical Vein Endothelial Cells (HUVECs) and induce angiogenesis by directly targeting PTEN [30, 31]. Moreover, miR-21a-3p and its downstream target E2F8 were further studied.…”

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

“…MiR-21 promotes tumorigenesis in MM, glioblastoma and prostate cancer via inhibition of pivotal tumor suppressors ( Figure 3 ) [ 33 , 40 , 49 , 50 , 72 , 114 , 115 ]. MiR-21 modifies the extracellular matrix by suppressing critical inhibitors of matrix metalloproteinases including TIMP3 and RECK [ 55 , 56 , 116 ].…”

“…In fact, increased expression of miR-21 enhances the invasive potential of MM cells through TIMP3 inhibition [ 56 ]. Furthermore, miR-21 induces tumor angiogenesis through targeting PTEN, activating AKT and ERK1/2 signaling, thereby enhancing HIF-1α and VEGF expression as well as by targeting FASLG and angiotensin II [ 115 , 117 , 118 , 119 , 120 ].…”

“…Cosmic radiation primarily consists of neutrons and gamma rays allowing high linear energy transfer (LET) [ 176 ], which stimulates miR-21 expression through the STAT3 pathway ( Figure 1 ) [ 177 , 178 ]. Ionizing radiation-induced miR-21 promotes EMT and angiogenesis by downregulation of PTEN [ 115 , 179 ]. Notably, ionizing radiation causes bystander effects on neighboring non-irradiated cells via transfer of exosomes enriched in miR-21 [ 180 , 181 ].…”

MicroRNA: a novel implication for damage and protection against ionizing radiation

“…Additionally, miR-21, the star oncomiRNA, has been reported to perform its pro-tumor function in conjunction with radiation (Liu et al 2011 ). Zhang et al ( 2019 ) had identified a functional link between IR-inducible miR-21 and angiogenesis that promotes metastasis, invasion and growth of tumors. Ionizing radiation induced miR-21 overexpression, which in turn downregulated expression of PTEN and finally induced angiogenesis via increased vascular endothelial growth factor A (VEGF) and HIF-1α expression through the PI3K/AKT pathway.…”