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Published on: September 5, 2017
MicroRNA expression after ionizing radiation in human endothelial cells
Mechthild Wagner-Ecker1, Christian Schwager, Ute Wirkner
1Department of Radiation Oncology, German Cancer Research Center and University of Heidelberg Medical Center, Heidelberg, Germany. mejo.ecker@t-online.de
Radiation Oncology (London, England)
|March 30, 2010
Summary
Ionizing radiation alters microRNA (miRNA) expression in human endothelial cells, affecting cell growth and radiosensitivity. Specific miRNAs, like let-7g and miR-189, play key roles in the endothelial cell response to radiation.
Area of Science:
- Molecular Biology
- Radiation Oncology
- Cell Biology
Background:
- Endothelial cells (EC) are crucial radiotherapy targets in both normal and tumor tissues.
- MicroRNAs (miRNAs) are key regulators of gene expression and cellular processes.
- Understanding miRNA roles in endothelial cells post-radiation is vital for radiotherapy optimization.
Purpose of the Study:
- To investigate the impact of ionizing radiation on miRNA expression in primary human dermal microvascular endothelial cells (HDMEC).
- To functionally analyze the role of radiation-responsive miRNAs in endothelial cell survival and proliferation.
- To determine if differentially expressed miRNAs influence endothelial cell radiosensitivity.
Main Methods:
- HDMEC were exposed to 2 Gy radiation, and miRNA expression was profiled using oligo-microarrays (361 miRNAs).
- Functional studies involved transfecting cells with miRNA precursors or inhibitors.
- Clonogenic survival and proliferation assays were conducted to assess cellular responses.
Main Results:
- Ionizing radiation altered the expression of several miRNAs, including up-regulation of let-7g, miR-16, miR-20a, miR-21, miR-29c and down-regulation of miR-18a, miR-125a, miR-127, miR-148b, miR-189, miR-503.
- Overexpression or inhibition of let-7g, miR-189, and miR-20a significantly impacted cell clonogenic survival and proliferation.
- Differential expression of miR-125a, miR-127, miR-189, and let-7g modulated HDMEC radiosensitivity, with miR-125a and miR-189 showing radioprotective effects, while miR-127 and let-7g enhanced radiosensitivity.
Conclusions:
- Ionizing radiation induces significant changes in miRNA profiles within human endothelial cells.
- These radiation-responsive miRNAs demonstrably influence endothelial cell growth, clonogenicity, and radiosensitivity.
- The findings suggest that miRNAs are integral components of the endothelium's innate response to radiation, potentially serving as therapeutic targets.
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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