Identification of Thyroid Genes Whose Expression Is Altered by Neonatal Irradiation in Rats

TL;DR

This study identifies genes in rat thyroids that are altered by early-life radiation exposure, which may explain increased cancer risk in children.

Contribution

The study identifies specific genes altered by neonatal irradiation that may contribute to thyroid cancer susceptibility in young individuals.

Findings

Five genes were upregulated and one gene was downregulated in neonatally irradiated rat thyroids.

Changes in CPA4 and CRTAC1 gene expression were confirmed at the protein level.

The altered gene expression patterns were also observed in thyroid tumors caused by an iodine-deficient diet.

Abstract

Childhood radiation is a risk factor for thyroid cancer that became well known after the Chernobyl nuclear plant accident. Although these human cases have been extensively studied, the mechanisms underlying childhood susceptibility to radiation-induced thyroid cancer have yet to be explained. Our previous study showed that neonatal X-irradiation resulted in long-term alterations in the mRNA expression of thyroid cancer-related marker genes, which may be a critical mechanism for understanding the higher radiation sensitivity in young patients. In this study, RNA sequencing (RNA-Seq)-based gene expression analysis was employed to identify thyroid genes whose mRNA expression was changed by neonatal irradiation. Male Wistar rats aged 1 week and 4 months were subjected to cervical X-irradiation at 4 Gy. After 8 weeks, total RNA was extracted from the thyroid and subjected to RNA-Seq analysis to identify differentially expressed genes following irradiation. We identified five upregulated genes (i.e., Adm2, Vnn1, Snph, Gria3, and Cpa4) and one downregulated gene (i.e., Crtac1) explicitly altered by neonatal radiation exposure. Western blotting confirmed the corresponding changes in CPA4 and CRTAC1 expression. The gene expressions identified were also altered in thyroid tumors induced by an iodine-deficient diet. These long-term changes in thyroid gene expression caused by neonatal irradiation may be involved in the increased risk of thyroid carcinogenesis.

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