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Published on: May 27, 2016
Ionizing Radiation-inducible microRNA-21 Induces Angiogenesis by Directly Targeting PTEN
Yongchun Zhang1, Zhiying Chen1, Lingxin Feng1
1Department of Radiotherapy, Affiliated Hospital of Qingdao University, Qingdao, China.
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.
Insights
Ionizing radiation (IR) increases tumor cell proliferation and migration by upregulating microRNA-21 (miR-21). This microRNA targets PTEN, inhibiting its expression and promoting tumor growth, suggesting miR-21 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Radiation Biology
Background:
- MicroRNAs (miRNAs) play roles as oncogenes or tumor suppressors.
- The impact of ionizing radiation (IR) on miRNA expression and tumor cell behavior needs further study.
Purpose of the Study:
- Investigate the effects of IR on miRNA expression and tumor cell biological behavior.
- Determine the role of miR-21 in IR-induced changes in HUVEC cells.
Main Methods:
- Assessed HUVEC cell proliferation, migration, and tube formation after IR.
- Measured miR-21, VEGF, and HIF-1α levels using Western blot.
- Investigated miR-21's effect on PTEN expression via RT-PCT and Western blot.
Main Results:
- IR and miR-21 both enhanced HUVEC cell proliferation, migration, and tube formation.
- IR increased miR-21 expression, inhibiting PTEN and accumulating VEGF/HIF-1α via the PI3K/AKT pathway.
- Restoring PTEN expression counteracted IR-induced tumor cell changes.
Conclusions:
- miR-21 promotes tumor cell proliferation and migration by targeting and inhibiting PTEN.
- miR-21 emerges as a potential therapeutic target for cancer treatment.
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