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Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2

Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overex...

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Autores principales: Yawut, Natpaphan, Cho, Il-Rae, Budluang, Phatcharaporn, Kaowinn, Sirichat, Kaewpiboon, Chutima, Jeon, Byeoleun, Kim, Sang-Woo, Kang, Ho Young, Kang, Min-Kyung, Koh, Sang Seok, Chung, Young-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774111/
https://www.ncbi.nlm.nih.gov/pubmed/35053270
http://dx.doi.org/10.3390/biom12010122
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author Yawut, Natpaphan
Cho, Il-Rae
Budluang, Phatcharaporn
Kaowinn, Sirichat
Kaewpiboon, Chutima
Jeon, Byeoleun
Kim, Sang-Woo
Kang, Ho Young
Kang, Min-Kyung
Koh, Sang Seok
Chung, Young-Hwa
author_facet Yawut, Natpaphan
Cho, Il-Rae
Budluang, Phatcharaporn
Kaowinn, Sirichat
Kaewpiboon, Chutima
Jeon, Byeoleun
Kim, Sang-Woo
Kang, Ho Young
Kang, Min-Kyung
Koh, Sang Seok
Chung, Young-Hwa
author_sort Yawut, Natpaphan
collection PubMed
description Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overexpression of CUG2 on microRNA levels using a microRNA microarray. Levels of miR-3656 were decreased when CUG2 was overexpressed; on the basis of this result, we further examined the target proteins of this microRNA. We focused on Jumonji C domain-containing protein 5 (JMJD5), as it has not been previously reported to be targeted by miR-3656. When CUG2 was overexpressed, JMJD5 expression was upregulated compared to that in control cells. A 3′ untranslated region (UTR) assay revealed that an miR-3656 mimic targeted the JMJD5 3′UTR, but the miR-3656 mimic failed to target a mutant JMJD5 3′UTR, indicating that miR-3656 targets the JMJD5 transcript. Administration of the miR-3656 mimic decreased the protein levels of JMD5 according to Western blotting. Additionally, the miR-3656 mimic decreased CUG2-induced cell migration, evasion, and sphere formation and sensitized the cells to doxorubicin. Suppression of JMJD5, with its small interfering RNA, impeded CUG2-induced cancer stem cell-like phenotypes. Thus, overexpression of CUG2 decreases miR-3656 levels, leading to upregulation of JMJD5, eventually contributing to cancer stem cell-like phenotypes.
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spelling pubmed-87741112022-01-21 Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2 Yawut, Natpaphan Cho, Il-Rae Budluang, Phatcharaporn Kaowinn, Sirichat Kaewpiboon, Chutima Jeon, Byeoleun Kim, Sang-Woo Kang, Ho Young Kang, Min-Kyung Koh, Sang Seok Chung, Young-Hwa Biomolecules Article Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overexpression of CUG2 on microRNA levels using a microRNA microarray. Levels of miR-3656 were decreased when CUG2 was overexpressed; on the basis of this result, we further examined the target proteins of this microRNA. We focused on Jumonji C domain-containing protein 5 (JMJD5), as it has not been previously reported to be targeted by miR-3656. When CUG2 was overexpressed, JMJD5 expression was upregulated compared to that in control cells. A 3′ untranslated region (UTR) assay revealed that an miR-3656 mimic targeted the JMJD5 3′UTR, but the miR-3656 mimic failed to target a mutant JMJD5 3′UTR, indicating that miR-3656 targets the JMJD5 transcript. Administration of the miR-3656 mimic decreased the protein levels of JMD5 according to Western blotting. Additionally, the miR-3656 mimic decreased CUG2-induced cell migration, evasion, and sphere formation and sensitized the cells to doxorubicin. Suppression of JMJD5, with its small interfering RNA, impeded CUG2-induced cancer stem cell-like phenotypes. Thus, overexpression of CUG2 decreases miR-3656 levels, leading to upregulation of JMJD5, eventually contributing to cancer stem cell-like phenotypes. MDPI 2022-01-12 /pmc/articles/PMC8774111/ /pubmed/35053270 http://dx.doi.org/10.3390/biom12010122 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yawut, Natpaphan
Cho, Il-Rae
Budluang, Phatcharaporn
Kaowinn, Sirichat
Kaewpiboon, Chutima
Jeon, Byeoleun
Kim, Sang-Woo
Kang, Ho Young
Kang, Min-Kyung
Koh, Sang Seok
Chung, Young-Hwa
Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title_full Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title_fullStr Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title_full_unstemmed Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title_short Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2
title_sort elevated expression of jmjd5 protein due to decreased mir-3656 levels contributes to cancer stem cell-like phenotypes under overexpression of cancer upregulated gene 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774111/
https://www.ncbi.nlm.nih.gov/pubmed/35053270
http://dx.doi.org/10.3390/biom12010122
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