ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a

Jin Gu Cho, Seho Park, Chae Hyun Lim, Hong Sook Kim, Seung Yong Song, Tae Young Roh, Jong Hyuk Sung, Wonhee Suh, Seok Jin Ham, Key Hwan Lim, Sang Gyu Park

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

ZNF224 is a Krüppel-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.

Original languageEnglish
Pages (from-to)31177-31190
Number of pages14
JournalOncotarget
Volume7
Issue number21
DOIs
Publication statusPublished - 2016 May 24

All Science Journal Classification (ASJC) codes

  • Oncology

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    Cho, J. G., Park, S., Lim, C. H., Kim, H. S., Song, S. Y., Roh, T. Y., Sung, J. H., Suh, W., Ham, S. J., Lim, K. H., & Park, S. G. (2016). ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a. Oncotarget, 7(21), 31177-31190. https://doi.org/10.18632/oncotarget.8870