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

13 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

Fingerprint

Zinc Fingers
Down-Regulation
Consensus Sequence
Apoptosis
Growth
Genes
Carcinoma, Ductal, Breast
Co-Repressor Proteins
Proteins
3' Untranslated Regions
Luciferases
Cell Survival
Enzyme-Linked Immunosorbent Assay
Breast Neoplasms
DNA
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

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. / ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a. In: Oncotarget. 2016 ; Vol. 7, No. 21. pp. 31177-31190.
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abstract = "ZNF224 is a Kr{\"u}ppel-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.",
author = "Cho, {Jin Gu} and Seho Park and Lim, {Chae Hyun} and Kim, {Hong Sook} and Song, {Seung Yong} and Roh, {Tae Young} and Sung, {Jong Hyuk} and Wonhee Suh and Ham, {Seok Jin} and Lim, {Key Hwan} and Park, {Sang Gyu}",
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Cho, JG, Park, S, Lim, CH, Kim, HS, Song, SY, Roh, TY, Sung, JH, Suh, W, Ham, SJ, Lim, KH & Park, SG 2016, 'ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a', Oncotarget, vol. 7, no. 21, pp. 31177-31190. https://doi.org/10.18632/oncotarget.8870

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

In: Oncotarget, Vol. 7, No. 21, 24.05.2016, p. 31177-31190.

Research output: Contribution to journalArticle

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T1 - ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a

AU - Cho, Jin Gu

AU - Park, Seho

AU - Lim, Chae Hyun

AU - Kim, Hong Sook

AU - Song, Seung Yong

AU - Roh, Tae Young

AU - Sung, Jong Hyuk

AU - Suh, Wonhee

AU - Ham, Seok Jin

AU - Lim, Key Hwan

AU - Park, Sang Gyu

PY - 2016/5/24

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AB - 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.

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