{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:53:51Z","timestamp":1760057631700,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS Kakenhi","doi-asserted-by":"publisher","award":["24K11680"],"award-info":[{"award-number":["24K11680"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Research Grant from the network-type joint Usage\/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, and Fukushima Medical University","award":["24K11680"],"award-info":[{"award-number":["24K11680"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26051874","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:22:31Z","timestamp":1740140551000},"page":"1874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Thyroid Genes Whose Expression Is Altered by Neonatal Irradiation in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-4001","authenticated-orcid":false,"given":"Nariaki","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsumi","family":"Matsuu-Matsuyama","sequence":"additional","affiliation":[{"name":"Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-8735","authenticated-orcid":false,"given":"Masahiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Drozdovitch, V. (2021). Radiation Exposure to the Thyroid After the Chernobyl Accident. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.569041"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.14310\/horm.2002.1234","article-title":"Radioactivity and thyroid cancer","volume":"8","author":"Reiners","year":"2009","journal-title":"Hormones"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/ijc.27749","article-title":"Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure","volume":"132","author":"Furukawa","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1148\/83.3.501","article-title":"The Latent Interval for Thyroid Cancer Following Irradiation","volume":"83","author":"Raventos","year":"1964","journal-title":"Radiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1289\/ehp.1002674","article-title":"I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident","volume":"119","author":"Brenner","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/aje\/kwm301","article-title":"A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Dose-Response Analysis of Thyroid Follicular Adenomas Detected during First Screening in Ukraine (1998\u20132000)","volume":"167","author":"Zablotska","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2307\/3572786","article-title":"Effect of Age on the Iodine-131 Metabolism and the Radiation Sensitivity of the Rat Thyroid","volume":"38","author":"Sikov","year":"1969","journal-title":"Radiat. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000437263","article-title":"Thyroid Growth and Cancer","volume":"4","author":"Williams","year":"2015","journal-title":"Eur. Thyroid. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.7150\/ijms.29935","article-title":"Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations","volume":"16","author":"Abdullah","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/rpd\/ncy146","article-title":"RADIATION AND THYROID CANCER\u2014AN OVERVIEW","volume":"182","author":"Thomas","year":"2018","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"330","DOI":"10.2307\/3574824","article-title":"Radiation-Induced Thyroid Tumors in Infant Rats","volume":"73","author":"Christov","year":"1978","journal-title":"Radiat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1507\/endocrj.EJ19-0245","article-title":"Morphological and functional changes in neonatally X-irradiated thyroid gland in rats","volume":"67","author":"Fujimoto","year":"2020","journal-title":"Endocr. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fujimoto, N., Matsuu-Matsuyama, M., and Nakashima, M. (2021). Single neonatal irradiation induces long-term gene expression changes in the thyroid gland, which may be involved in the tumorigenesis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-03012-5"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/bioinformatics\/btz854","article-title":"RaNA-Seq: Interactive RNA-Seq analysis from FASTQ files to functional analysis","volume":"36","author":"Prieto","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1289\/ehp.1205783","article-title":"Measures of Thyroid Function among Belarusian Children and Adolescents Exposed to Iodine-131 from the Accident at the Chernobyl Nuclear Plant","volume":"121","author":"Ostroumova","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1088\/0952-4746\/26\/2\/001","article-title":"Cancer consequences of the Chernobyl accident: 20 years on","volume":"26","author":"Cardis","year":"2006","journal-title":"J. Radiol. Prot."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1667\/RR14213.1","article-title":"Thyroid cancer after childhood exposure to external radiation: An updated pooled analysis of 12 studies","volume":"185","author":"Veiga","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"i78","DOI":"10.1093\/jrr\/rraa139","article-title":"Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis","volume":"62","author":"Kurohama","year":"2021","journal-title":"J. Radiat. Res."},{"key":"ref_19","first-page":"1256","article-title":"Thyroid cell proliferation in rats and induction of tumors by X-rays","volume":"35","author":"Christov","year":"1975","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0021-9975(08)80163-6","article-title":"Incidence and morphology of spontaneous thyroid tumours in different strains of rats","volume":"102","author":"Wiese","year":"1990","journal-title":"J. Comp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1158\/0008-5472.CAN-18-0595","article-title":"Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements","volume":"78","author":"Seo","year":"2018","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.ajpath.2019.02.009","article-title":"Syntaphilin Is a Novel Biphasic Biomarker of Aggressive Prostate Cancer and a Metastasis Predictor","volume":"189","author":"Hwang","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/bph.13814","article-title":"Adrenomedullin 2\/intermedin: A putative drug candidate for treatment of cardiometabolic diseases","volume":"175","author":"Zhang","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mce.2014.07.008","article-title":"Induction of adrenomedullin 2\/intermedin expression by thyroid stimulating hormone in thyroid","volume":"395","author":"Nagasaki","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/path.5997","article-title":"Adrenomedullin2 stimulates progression of thyroid cancer in mice and humans under nutrient excess conditions","volume":"258","author":"Kim","year":"2022","journal-title":"J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bartucci, R., Salvati, A., Olinga, P., and Boersma, Y.L. (2019). Vanin 1: Its Physiological Function and Role in Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163891"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Guan, W., Xu, J., Shi, Y., Wang, X., Gu, S., and Xie, L. (2023). VNN1 as a potential biomarker for sepsis diagnosis and its implications in immune infiltration and tumor prognosis. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1236484"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate Receptor Ion Channels: Structure, Regulation, and Function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Andersson, B., Langen, B., Liu, P., and L\u00f3pez, M.D. (2023). Development of a machine learning framework for radiation biomarker discovery and absorbed dose prediction. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1156009"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bademler, S., Ucuncu, M.Z., Yasasever, C.T., Serilmez, M., Ertin, H., and Karanl\u0131k, H. (2019). Diagnostic and Prognostic Significance of Carboxypeptidase A4 (CPA4) in Breast Cancer. Biomolecules, 9.","DOI":"10.3390\/biom9030103"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.21037\/jgo-22-987","article-title":"Knockdown of carboxypeptidase A4 (CPA4) inhibits gastric cancer cell progression via cell cycle arrest and apoptosis","volume":"13","author":"Lei","year":"2022","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1089\/thy.2023.0427","article-title":"Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer","volume":"34","author":"Choi","year":"2024","journal-title":"Thyroid"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, W.-M., Chan, T.-C., Wei, Y.-C., Li, C.-F., Ke, H.-L., Wu, W.-J., Hsu, C.-C., Wang, S.-C., and Yeh, C.-F. (2023). Downregulation of CRTAC1 in Urothelial Carcinoma Promotes Tumor Aggressiveness and Confers Poor Prognosis. Front. Biosci., 28.","DOI":"10.31083\/j.fbl2809217"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tan, L., Zhang, H., Ding, Y., Huang, Y., and Sun, D. (2024). CRTAC1 identified as a promising diagnosis and prognostic biomarker in lung adenocarcinoma. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-61804-x"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9377","DOI":"10.1080\/21655979.2021.1974645","article-title":"CRTAC1 (Cartilage acidic protein 1) inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer by downregulating Yin Yang 1 (YY1) to inactivate the TGF-beta pathway","volume":"12","author":"Yang","year":"2021","journal-title":"Bioengineered"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Matsuu-Matsuyama, M., Shichijo, K., Matsuda, K., Fujimoto, N., Kondo, H., Miura, S., Kurashige, T., Nagayama, Y., and Nakashima, M. (2021). Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98481-z"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Meadows, S.K., Dressman, H.K., Muramoto, G.G., Himburg, H., Salter, A., Wei, Z., Ginsburg, G.S., Chao, N.J., Nevins, J.R., and Chute, J.P. (2008). Gene expression signatures of radiation response are specific, durable and accurate in mice and humans. PLoS ONE, 3.","DOI":"10.1371\/annotation\/83c37842-8867-4cfb-a271-9e4bf36fb9b8"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1667\/RR14044.1","article-title":"Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model","volume":"184","author":"Paul","year":"2015","journal-title":"Radiat. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111723","DOI":"10.1016\/j.mrfmmm.2020.111723","article-title":"The long-term effects of exposure to ionising radiation on gene expression in mice","volume":"821","author":"Jafer","year":"2020","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1667\/RR2888.1","article-title":"Radiation-Induced Human Endogenous Retrovirus (HERV)-R env Gene Expression by Epigenetic Control","volume":"178","author":"Lee","year":"2012","journal-title":"Radiat. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Seong, K.M., and Cenci, G. (2022). Editorial: The Genetic and Epigenetic Bases of Cellular Response to Ionizing Radiation. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.857168"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Larsson, M., Rudqvist, N., Spetz, J., Shubbar, E., Parris, T.Z., Langen, B., Helou, K., and Forssell-Aronsson, E. (2020). Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0244098"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:40:12Z","timestamp":1760028012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/1874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26051874"],"URL":"https:\/\/doi.org\/10.3390\/ijms26051874","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,2,21]]}}}