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Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer
BACKGROUND: Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097102/ https://www.ncbi.nlm.nih.gov/pubmed/35550582 http://dx.doi.org/10.1186/s12935-022-02606-x |
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author | Kim, Ga Hyun Heo, Hye Jin Kang, Ji Wan Kim, Eun-Kyung Baek, Seung Eun Kim, Keunyoung Kim, In Joo Suh, Sunghwan Lee, Byung-Joo Kim, Yun Hak Pak, Kyoungjune |
author_facet | Kim, Ga Hyun Heo, Hye Jin Kang, Ji Wan Kim, Eun-Kyung Baek, Seung Eun Kim, Keunyoung Kim, In Joo Suh, Sunghwan Lee, Byung-Joo Kim, Yun Hak Pak, Kyoungjune |
author_sort | Kim, Ga Hyun |
collection | PubMed |
description | BACKGROUND: Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. METHODS: We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues. RESULTS: We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. CONCLUSIONS: Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02606-x. |
format | Online Article Text |
id | pubmed-9097102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90971022022-05-13 Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer Kim, Ga Hyun Heo, Hye Jin Kang, Ji Wan Kim, Eun-Kyung Baek, Seung Eun Kim, Keunyoung Kim, In Joo Suh, Sunghwan Lee, Byung-Joo Kim, Yun Hak Pak, Kyoungjune Cancer Cell Int Primary Research BACKGROUND: Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. METHODS: We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues. RESULTS: We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. CONCLUSIONS: Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02606-x. BioMed Central 2022-05-12 /pmc/articles/PMC9097102/ /pubmed/35550582 http://dx.doi.org/10.1186/s12935-022-02606-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Kim, Ga Hyun Heo, Hye Jin Kang, Ji Wan Kim, Eun-Kyung Baek, Seung Eun Kim, Keunyoung Kim, In Joo Suh, Sunghwan Lee, Byung-Joo Kim, Yun Hak Pak, Kyoungjune Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title | Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title_full | Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title_fullStr | Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title_full_unstemmed | Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title_short | Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer |
title_sort | multi-omics analysis revealed tek and axin2 are potential biomarkers in multifocal papillary thyroid cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097102/ https://www.ncbi.nlm.nih.gov/pubmed/35550582 http://dx.doi.org/10.1186/s12935-022-02606-x |
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