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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
Author(s)
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
Date Issued
January 1, 2022
Type
Article
Abstract
Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phe-notypes, 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′ un-translated 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.
Citation
Biomolecules, 12(1), 2022