Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs

A novel mechanism of tissue radioprotection by flaxseed

Melpo Christofidou-Solomidou, Ralph Pietrofesa, Evguenia Arguiri, Melissa A. McAlexander, Kenneth Whitaker Witwer

Research output: Contribution to journalArticle

Abstract

Introduction: Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. Methods: In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. Results: FS significantly modulated expression of multiple miRNAs, including 7 with P <0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10-to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence-and apoptosis-related factors. Conclusions: FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.

Original languageEnglish (US)
Pages (from-to)930-937
Number of pages8
JournalCancer Biology and Therapy
Volume15
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Flax
MicroRNAs
Lung
Radiation
X-Rays
RNA
Diet
Thorax
Down-Regulation
Dietary Supplements
Oligonucleotides
Lung Diseases
Anti-Inflammatory Agents
Radiotherapy
Therapeutics
Antioxidants

Keywords

  • Antioxidant
  • Flaxseed
  • Inflammation
  • Lung fibrosis
  • Lung injury
  • MiR-150
  • MiR-29c
  • MiR-34a
  • MiRNA
  • Mouse model
  • Radiation pneumonopathy
  • ROS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs : A novel mechanism of tissue radioprotection by flaxseed. / Christofidou-Solomidou, Melpo; Pietrofesa, Ralph; Arguiri, Evguenia; McAlexander, Melissa A.; Witwer, Kenneth Whitaker.

In: Cancer Biology and Therapy, Vol. 15, No. 7, 2014, p. 930-937.

Research output: Contribution to journalArticle

Christofidou-Solomidou, Melpo ; Pietrofesa, Ralph ; Arguiri, Evguenia ; McAlexander, Melissa A. ; Witwer, Kenneth Whitaker. / Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs : A novel mechanism of tissue radioprotection by flaxseed. In: Cancer Biology and Therapy. 2014 ; Vol. 15, No. 7. pp. 930-937.
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abstract = "Introduction: Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. Methods: In this exploratory pilot study, mice were fed 10{\%} FS or a 0{\%} FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. Results: FS significantly modulated expression of multiple miRNAs, including 7 with P <0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10-to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50{\%} decrease of the p53-responsive miR-34a, which regulates senescence-and apoptosis-related factors. Conclusions: FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.",
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T1 - Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs

T2 - A novel mechanism of tissue radioprotection by flaxseed

AU - Christofidou-Solomidou, Melpo

AU - Pietrofesa, Ralph

AU - Arguiri, Evguenia

AU - McAlexander, Melissa A.

AU - Witwer, Kenneth Whitaker

PY - 2014

Y1 - 2014

N2 - Introduction: Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. Methods: In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. Results: FS significantly modulated expression of multiple miRNAs, including 7 with P <0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10-to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence-and apoptosis-related factors. Conclusions: FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.

AB - Introduction: Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. Methods: In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. Results: FS significantly modulated expression of multiple miRNAs, including 7 with P <0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10-to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence-and apoptosis-related factors. Conclusions: FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.

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KW - MiRNA

KW - Mouse model

KW - Radiation pneumonopathy

KW - ROS

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