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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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.
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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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