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2016 ; 7
(10
): 11412-23
Nephropedia Template TP
gab.com Text
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Oncogenic potential of histone-variant H2A Z 1 and its regulatory role in cell
cycle and epithelial-mesenchymal transition in liver cancer
#MMPMID26863632
Yang HD
; Kim PJ
; Eun JW
; Shen Q
; Kim HS
; Shin WC
; Ahn YM
; Park WS
; Lee JY
; Nam SW
Oncotarget
2016[Mar]; 7
(10
): 11412-23
PMID26863632
show ga
H2A.Z is a highly conserved H2A variant, and two distinct H2A.Z isoforms, H2A.Z.1
and H2A.Z.2, have been identified as products of two non-allelic genes, H2AFZ and
H2AFV. H2A.Z has been reported to be overexpressed in breast, prostate and
bladder cancers, but most studies did not clearly distinguish between isoforms.
One recent study reported a unique role for the H2A.Z isoform H2A.Z.2 as a driver
of malignant melanoma. Here we first report that H2A.Z.1 plays a pivotal role in
the liver tumorigenesis by selectively regulating key molecules in cell cycle and
epithelial-mesenchymal transition (EMT). H2AFZ expression was significantly
overexpressed in a large cohort of hepatocellular carcinoma (HCC) patients, and
high expression of H2AFZ was significantly associated with their poor prognosis.
H2A.Z.1 overexpression was demonstrated in a subset of human HCC and cell lines.
H2A.Z.1 knockdown suppressed HCC cell growth by transcriptional deregulation of
cell cycle proteins and caused apoptotic cell death of HCC cells. We also
observed that H2A.Z.1 knockdown reduced the metastatic potential of HCC cells by
selectively modulating epithelial-mesenchymal transition regulatory proteins such
as E-cadherin and fibronectin. In addition, H2A.Z.1 knockdown reduced the in vivo
tumor growth rate in a mouse xenograft model. In conclusion, our findings suggest
the oncogenic potential of H2A.Z.1 in liver tumorigenesis and that it plays
established role in accelerating cell cycle transition and EMT during
hepatocarcinogenesis. This makes H2A.Z.1 a promising target in liver cancer
therapy.