PMID- 22580414
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20191028
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 62
IP  - 6
DP  - 2013 Jun
TI  - Zinc-finger protein 545 is a novel tumour suppressor that acts by inhibiting 
      ribosomal RNA transcription in gastric cancer.
PG  - 833-41
LID - 10.1136/gutjnl-2011-301776 [doi]
AB  - OBJECTIVE: Zinc-finger protein 545 (ZNF545) is a member of the family of 
      Kruppel-associated box-containing zinc-finger proteins. The aim of this study was 
      to clarify its biological function as a tumour suppressor in gastric cancer. 
      DESIGN: The biological function of ZNF545 was determined by cell growth and 
      apoptosis assays. The ZNF545 target signal pathway was identified by promoter 
      luciferase assay, northern blot, run-on transcription assay, chromatin 
      immunoprecipitation and coimmunoprecipitation assays. The clinical application of 
      ZNF545 was assessed in primary gastric cancers. RESULTS: ZNF545 was silenced or 
      reduced in 16 out of 18 gastric cancer cell lines by promoter hypermethylation. 
      Restoration of ZNF545 expression in gastric cancer cell lines suppressed cell 
      proliferation and induced apoptosis. These effects of ZNF545 were attributed to 
      inhibition of ribosomal RNA (rRNA) transcription. Inhibition of rRNA 
      transcription by ZNF545 was further revealed to be associated with direct 
      ribosomal DNA (rDNA) promoter binding, recruitment of the corepressor, 
      heterochromatin protein 1beta, and reduction of trimethylated histone H3 at the Lys4 
      residue at the rDNA locus. ZNF545 methylation was detected in 51.9% (41/79) of 
      gastric cancer tissues, 27.0% (20/74) of adjacent non-tumour gastric tissues 
      (p=0.001), but none of 20 normal controls. Multivariate analysis revealed that 
      patients with ZNF545 methylation had a significant decrease in overall survival. 
      Kaplan-Meier survival curves showed that ZNF545 methylation was significantly 
      associated with shortened survival in patients with stage I-II gastric cancer. 
      CONCLUSIONS: ZNF545 acts as a functional tumour suppressor in gastric cancer by 
      inhibiting rRNA transcription. Its methylation at early stages of gastric 
      carcinogenesis is an independent prognostic factor.
FAU - Wang, Shiyan
AU  - Wang S
AD  - Institute of Digestive Disease and Department of Medicine and Therapeutics, 
      Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong 
      Kong.
FAU - Cheng, Yingduan
AU  - Cheng Y
FAU - Du, Wan
AU  - Du W
FAU - Lu, Leina
AU  - Lu L
FAU - Zhou, Liang
AU  - Zhou L
FAU - Wang, Huating
AU  - Wang H
FAU - Kang, Wei
AU  - Kang W
FAU - Li, Xiaoxing
AU  - Li X
FAU - Tao, Qian
AU  - Tao Q
FAU - Sung, Joseph J Y
AU  - Sung JJ
FAU - Yu, Jun
AU  - Yu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120512
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Ribosomal)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (ZFP82 protein, human)
SB  - IM
CIN - Gut. 2015 Nov;64(11):1836-7. PMID: 26289056
MH  - Blotting, Northern
MH  - Cell Line, Tumor
MH  - DNA Methylation
MH  - DNA Primers/chemistry
MH  - Down-Regulation
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Humans
MH  - Immunoprecipitation
MH  - Kaplan-Meier Estimate
MH  - Nuclear Proteins/*physiology
MH  - Prognosis
MH  - RNA Interference/physiology
MH  - RNA, Ribosomal/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Stomach Neoplasms/*genetics/mortality/physiopathology
MH  - *Transcription, Genetic
MH  - Tumor Suppressor Proteins/*physiology
MH  - Zinc Fingers/physiology
EDAT- 2012/05/15 06:00
MHDA- 2013/07/03 06:00
CRDT- 2012/05/15 06:00
PHST- 2012/05/15 06:00 [entrez]
PHST- 2012/05/15 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
AID - gutjnl-2011-301776 [pii]
AID - 10.1136/gutjnl-2011-301776 [doi]
PST - ppublish
SO  - Gut. 2013 Jun;62(6):833-41. doi: 10.1136/gutjnl-2011-301776. Epub 2012 May 12.