Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism

doi:10.1016/j.bbrc.2008.09.080

Biochemical and Biophysical Research Communications

Volume 377, Issue 1, 5 December 2008, Pages 41-45

https://doi.org/10.1016/j.bbrc.2008.09.080 Get rights and content

Abstract

To investigate involvement of miRNAs in radiation responses we used microRNAome profiling to analyze the sex-specific response of radiation sensitive hematopoietic lymphoid tissues. We show that radiation exposure resulted in a significant and sex-specific deregulation of microRNA expression in murine spleen and thymus tissues. Among the regulated miRNAs, we found that changes in expression of miR-34a and miR-7 may be involved in important protective mechanisms counteracting radiation cytotoxicity. We observed a significant increase in the expression of tumor-suppressor miR-34a, paralleled by a decrease in the expression of its target oncogenes NOTCH1, MYC, E2F3 and cyclin D1. Additionally, we show that miR-7 targets the lymphoid–specific helicase LSH, a pivotal regulator of DNA methylation and genome stability. While miR-7 was significantly down-regulated LSH was significantly up-regulated. These cellular changes may constitute an attempt to counteract radiation-induced hypomethylation. Tissue specificity of miRNA responses and possible regulation of miRNA expression upon irradiation are discussed.

Section snippets

Materials and methods

Model. In this study, we utilized an in vivo mouse model to study microRNAome changes in the thymus and spleen of male and female animals following IR exposure. The C57BL/6 mouse model is widely used, well characterized, and generally accepted for studies of IR-induced changes in hematopoietic lymphoid tissue [5]. Handling and care of animals was in accordance with the recommendations of the Canadian Council for Animal Care and Use.

Radiation exposure. Fifty-day-old C57BL/6 mice (10 males and 10

Results & discussion

In this study, we utilized an in vivo murine model to analyze and compare microRNAome changes induced by exposure to X-rays in the lymphoid hematopoietic spleen and thymus tissue of male and female mice. Equal cohorts of male and female experimental animals were divided in two experimental groups, ‘exposed’ animals (2.5 Gy of whole-body X-ray irradiation) and sham treated ‘control’ animals.

Analysis of the murine spleen microRNAome revealed a number of intriguing patterns. In male spleen

Acknowledgments

We are grateful to Karen Dow-Cazal and Charlotte Holmes for animal care. We appreciate the help of Dr. Valentina Titova in proofreading this manuscript. This research was supported by ACB and CIHR operating grants to Olga Kovalchuk. Igor Koturbash is the recipient of the Dr. Cyril Kay Alberta Cancer Board (ACB) Graduate Scholarship. Olga Kovalchuk is a CIHR Research Chair in Gender and Health.

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View full text

Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism

Abstract

Section snippets

Materials and methods

Results & discussion

Acknowledgments

Semin. Oncol.

Semin. Oncol.

Blood

Mutat. Res.

FEBS Lett.

Cell

Int. J. Radiat. Oncol. Biol. Phys.

Eur. J. Cancer

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Exp. Hematol.

Radiation carcinogenesis

Carcinogenesis

Malignant diseases of hematopoietic and lymphpoid tissues in chernobyl clean-up workers

Hematol. J.

Cancer risks among radiologists and radiologic technologists: review of epidemiologic studies

Radiology

The dose-response relationships for myeloid leukemia and malignant lymphoma in BC3F1 mice

Radiat. Res.

T lymphoid and mixed lineage thymic lymphomas in the irradiated mouse

Carcinogenesis

Epigenetics in human disease and prospects for epigenetic therapy

Nature

MicroRNAs in cell proliferation, cell death, and tumorigenesis

Br. J. Cancer