ZNF224, Krüppel like zinc finger protein, induces cell growth and apoptosis-resistance by down-regulation of p21 and p53 via miR-663a.
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.
Department of Biomedical Science, CHA University, Sungnam-si, Gyunggi-do, Korea.|Laboratory for Tracing of Gene Function, Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, Gyunggi-do, Korea.
Jin Gu
JG
Cho
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
Seho
S
Park
Division of Integrative Biosciences & Biotechnology, Pohang University of Science & Technology (POSTECH), Pohang, Gyeongbuk, Korea.
Chae Hyun
CH
Lim
Laboratory for Tracing of Gene Function, Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, Gyunggi-do, Korea.
Hong Sook
HS
Kim
Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Korea.
Seung Yong
SY
Song
Division of Integrative Biosciences & Biotechnology, Pohang University of Science & Technology (POSTECH), Pohang, Gyeongbuk, Korea.
Tae-Young
TY
Roh
Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Korea.
Jong-Hyuk
JH
Sung
Department of Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Korea.
Wonhee
W
Suh
Division of Integrative Biosciences & Biotechnology, Pohang University of Science & Technology (POSTECH), Pohang, Gyeongbuk, Korea.
Seok-Jin
SJ
Ham
Laboratory for Tracing of Gene Function, Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, Gyunggi-do, Korea.
Key-Hwan
KH
Lim
Laboratory for Tracing of Gene Function, Department of Pharmacy, College of Pharmacy, Ajou University, Suwon, Gyunggi-do, Korea.
Sang Gyu
SG
Park
D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016158:Genes, p53; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C470003:ZNF224 protein, human
ZNF224; apoptosis; miR-663a; p21; p53