Differential expression of stress and immune response pathway transcripts and miRNAs in normal human endothelial cells subjected to fractionated or single-dose radiation.
Although modern radiotherapy technologies can precisely deliver higher doses of radiation to tumors, thus, reducing overall radiation exposure to normal tissues, moderate dose, and normal tissue toxicity still remains a significant limitation. The present study profiled the global effects on transcript and miR expression in human coronary artery endothelial cells using single-dose irradiation (SD, 10 Gy) or multifractionated irradiation (MF, 2 Gy × 5) regimens. Longitudinal time points were collected after an SD or final dose of MF irradiation for analysis using Agilent Human Gene Expression and miRNA microarray platforms. Compared with SD, the exposure to MF resulted in robust transcript and miR expression changes in terms of the number and magnitude. For data analysis, statistically significant mRNAs (2-fold) and miRs (1.5-fold) were processed by Ingenuity Pathway Analysis to uncover miRs associated with target transcripts from several cellular pathways after irradiation. Interestingly, MF radiation induced a cohort of mRNAs and miRs that coordinate the induction of immune response pathway under tight regulation. In addition, mRNAs and miRs associated with DNA replication, recombination and repair, apoptosis, cardiovascular events, and angiogenesis were revealed.


CONCLUSIONS
Radiation-induced alterations in stress and immune response genes in endothelial cells contribute to changes in normal tissue and tumor microenvironment, and affect the outcome of radiotherapy.
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and palayoor@mail.nih.gov.
Sanjeewani T
ST
Palayoor
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and.
Molykutty
M
John-Aryankalayil
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and.
Adeola Y
AY
Makinde
GenUs Biosystems, Inc., Northbrook, Illinois.
Michael T
MT
Falduto
GenUs Biosystems, Inc., Northbrook, Illinois.
Scott R
SR
Magnuson
Authors' Affiliations: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and.
C Norman
CN
Coleman
D017209:Apoptosis; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000378:metabolism* / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D013312:Stress, Physiological / Q000276:immunology
D035683:MicroRNAs