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Lucanthone, Autophagy Inhibitor, Enhances the Apoptotic Effects of TRAIL through miR-216a-5p-Mediated DR5 Upregulation and DUB3-Mediated Mcl-1 Downregulation

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Author(s)
Ji Yun YoonSeon Min WooSeung Un SeoSo Rae SongSeul Gi LeeTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Int J Mol Sci
Issued Date
2022
Volume
23
Issue
1
Keyword
DR5miR-216a-5pMcl-1DUB3
Abstract
A lucanthone, one of the family of thioxanthenones, has been reported for its inhibitory effects of apurinic endonuclease-1 and autophagy. In this study, we investigated whether lucanthone could enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in various cancer cells. Combined treatment with lucanthone and TRAIL significantly induced apoptosis in human renal carcinoma (Caki and ACHN), prostate carcinoma (PC3), and lung carcinoma (A549) cells. However, combined treatment did not induce apoptosis in normal mouse kidney cells (TCMK-1) and normal human skin fibroblast (HSF). Lucanthone downregulated protein expression of deubiquitinase DUB3, and a decreased expression level of DUB3 markedly led to enhance TRAIL-induced apoptosis. Ectopic expression of DUB3 inhibited combined treatment with lucanthone and TRAIL-induced apoptosis. Moreover, lucanthone increased expression level of DR5 mRNA via downregulation of miR-216a-5p. Transfection of miR-216a-5p mimics suppressed the lucanthone-induced DR5 upregulation. Taken together, these results provide the first evidence that lucanthone enhances TRAIL-induced apoptosis through DR5 upregulation by downregulation of miR-216a-5p and DUB3-dependent Mcl-1 downregulation in human renal carcinoma cells.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Ji Yun Yoon et al. (2022). Lucanthone, Autophagy Inhibitor, Enhances the Apoptotic Effects of TRAIL through miR-216a-5p-Mediated DR5 Upregulation and DUB3-Mediated Mcl-1 Downregulation. Int J Mol Sci, 23(1), 17. doi: 10.3390/ijms23010017
Type
Article
ISSN
1422-0067
Source
https://www.mdpi.com/1422-0067/23/1/17
DOI
10.3390/ijms23010017
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44125
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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