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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MDPI AG
2022-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/1/122 |
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| author | Natpaphan Yawut Il-Rae Cho Phatcharaporn Budluang Sirichat Kaowinn Chutima Kaewpiboon Byeoleun Jeon Sang-Woo Kim Ho Young Kang Min-Kyung Kang Sang Seok Koh Young-Hwa Chung |
| author_facet | Natpaphan Yawut Il-Rae Cho Phatcharaporn Budluang Sirichat Kaowinn Chutima Kaewpiboon Byeoleun Jeon Sang-Woo Kim Ho Young Kang Min-Kyung Kang Sang Seok Koh Young-Hwa Chung |
| author_sort | Natpaphan Yawut |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T01:49:59Z |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T01:49:59Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5ca7606e326c4ee9b9f538567b6931f62023-11-23T13:07:23ZengMDPI AGBiomolecules2218-273X2022-01-0112112210.3390/biom12010122Elevated Expression of JMJD5 Protein Due to Decreased miR-3656 Levels Contributes to Cancer Stem Cell-Like Phenotypes under Overexpression of Cancer Upregulated Gene 2Natpaphan Yawut0Il-Rae Cho1Phatcharaporn Budluang2Sirichat Kaowinn3Chutima Kaewpiboon4Byeoleun Jeon5Sang-Woo Kim6Ho Young Kang7Min-Kyung Kang8Sang Seok Koh9Young-Hwa Chung10BK21 Plus, Department of Cogno-Mechatronics Engineering, Optomechatronics Research Center, Pusan National University, Busan 46241, KoreaBK21 Plus, Department of Cogno-Mechatronics Engineering, Optomechatronics Research Center, Pusan National University, Busan 46241, KoreaBK21 Plus, Department of Cogno-Mechatronics Engineering, Optomechatronics Research Center, Pusan National University, Busan 46241, KoreaDepartment of General Science and Liberal Arts, Ladkrabang Prince of Chumphon Campus, King Mongkut’s Institute of Technology, Chumphon 86160, ThailandDepartment of Biology, Faculty of Science, Thaksin University, Patthalung 93210, ThailandDepartment of Biological Science, Pusan National University, Busan 46241, KoreaDepartment of Biological Science, Pusan National University, Busan 46241, KoreaDepartment of Microbiology, Pusan National University, Busan 46241, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaBK21 Plus, Department of Cogno-Mechatronics Engineering, Optomechatronics Research Center, Pusan National University, Busan 46241, KoreaOverexpression 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.https://www.mdpi.com/2218-273X/12/1/122cancer upregulated geneJumonji C domain-containing protein 5cancer stem cellmiR-3656 |
| spellingShingle | Natpaphan Yawut Il-Rae Cho Phatcharaporn Budluang Sirichat Kaowinn Chutima Kaewpiboon Byeoleun Jeon Sang-Woo Kim Ho Young Kang Min-Kyung Kang Sang Seok Koh Young-Hwa Chung 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 Biomolecules cancer upregulated gene Jumonji C domain-containing protein 5 cancer stem cell miR-3656 |
| 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 | cancer upregulated gene Jumonji C domain-containing protein 5 cancer stem cell miR-3656 |
| url | https://www.mdpi.com/2218-273X/12/1/122 |
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