ZNF224, Kruppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a
- Authors
- Cho, Jin Gu; Park, Seho; Lim, Chae Hyun; Kim, Hong Sook; Song, Seung Yong; Roh, Tae-Young; Sung, Jong-Hyuk; Suh, Wonhee; Ham, Seok-Jin; Lim, Key-Hwan; Park, Sang Gyu
- Issue Date
- 24-May-2016
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- ZNF224; miR-663a; p53; p21; apoptosis
- Citation
- ONCOTARGET, v.7, no.21, pp 31177 - 31190
- Pages
- 14
- Journal Title
- ONCOTARGET
- Volume
- 7
- Number
- 21
- Start Page
- 31177
- End Page
- 31190
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/6930
- DOI
- 10.18632/oncotarget.8870
- ISSN
- 1949-2553
1949-2553
- Abstract
- ZNF224 is a Kruppel-associated box-containing zinc-finger protein which represses gene transcription by interacting with various co-repressors. However, its consensus DNA sequences and target genes are not fully identified. In this study, we identified and characterized consensus DNA sequences containing 5'-CAGC-3' recognized by ZNF224 through ChIP-sequencing, which further confirmed by ELISA, SPR, qPCR, and luciferase activity assay. ZNF224 increased miR-663a transcription by binding to miR-663a promoter, which in turn binds to 3' UTR of p53 and p21 to decrease their expression. miR-663a antagonist abolished ZNF224-mediated suppression of p21 and p53, resulting in the enhanced apoptosis by CPT. The analyses using human breast ductal carcinoma tissues exhibited that the expression of ZNF224 and miR-663a was increased in cancer compared to non-cancer region. Consequently, ZNF224 increases cell survival and decreases apoptosis by decreasing the expression of p53 and p21 via miR-663a as a transcriptional activator. Taken together, we identified and characterized DNA binding element of ZNF224, and its target genes, miR-663a, which provides a novel insight in the down-regulation of p21 and p53 via miR-663a by ZNF224 in breast cancer.
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