Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs

Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression...

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Main Authors: MD Nazmul Hasan, MD Mahfuzur Rahman, Al Asmaul Husna, Daiki Kato, Takayuki Nakagawa, Mohammad Arif, Naoki Miura
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Veterinary Quarterly
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Online Access:https://www.tandfonline.com/doi/10.1080/01652176.2023.2300943
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author MD Nazmul Hasan
MD Mahfuzur Rahman
Al Asmaul Husna
Daiki Kato
Takayuki Nakagawa
Mohammad Arif
Naoki Miura
author_facet MD Nazmul Hasan
MD Mahfuzur Rahman
Al Asmaul Husna
Daiki Kato
Takayuki Nakagawa
Mohammad Arif
Naoki Miura
author_sort MD Nazmul Hasan
collection DOAJ
description Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.
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spelling doaj-art-39d512bdfc5c44e2878cbb779e182c162025-08-20T02:50:37ZengTaylor & Francis GroupVeterinary Quarterly0165-21761875-59412024-12-014411810.1080/01652176.2023.2300943Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogsMD Nazmul Hasan0MD Mahfuzur Rahman1Al Asmaul Husna2Daiki Kato3Takayuki Nakagawa4Mohammad Arif5Naoki Miura6Joint Graduate School of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, JapanDepartment of Human Oncology, University of WI School of Medicine and Public Health, Madison, WI, USAVeterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, Kagoshima, JapanLaboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo, JapanLaboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo, JapanJoint Graduate School of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, JapanJoint Graduate School of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, JapanHypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.https://www.tandfonline.com/doi/10.1080/01652176.2023.2300943HypoxiaY RNAdogmelanomanext-generation sequencing
spellingShingle MD Nazmul Hasan
MD Mahfuzur Rahman
Al Asmaul Husna
Daiki Kato
Takayuki Nakagawa
Mohammad Arif
Naoki Miura
Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
Veterinary Quarterly
Hypoxia
Y RNA
dog
melanoma
next-generation sequencing
title Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
title_full Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
title_fullStr Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
title_full_unstemmed Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
title_short Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs
title_sort hypoxia related y rna fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non metastatic oral melanoma in dogs
topic Hypoxia
Y RNA
dog
melanoma
next-generation sequencing
url https://www.tandfonline.com/doi/10.1080/01652176.2023.2300943
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