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2016 ; 35
(ä): 72
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TET3 inhibits TGF-?1-induced epithelial-mesenchymal transition by demethylating
miR-30d precursor gene in ovarian cancer cells
#MMPMID27141829
Ye Z
; Li J
; Han X
; Hou H
; Chen H
; Zheng X
; Lu J
; Wang L
; Chen W
; Li X
; Zhao L
J Exp Clin Cancer Res
2016[May]; 35
(ä): 72
PMID27141829
show ga
BACKGROUND: Abnormal DNA methylation/demethylation is recognized as a hallmark of
cancer. TET (ten-eleven translocation) family members are novel DNA demethylation
related proteins that dysregulate in multiple malignances. However, their effects
on ovarian cancer remain to be elucidated. METHODS: The changes of TET family
members during TGF-?1-induced epithelial-mesenchymal transition (EMT) in SKOV3
and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in
TGF-?1-treated ovarian cancer cells to examine its effect on TGF-?1-induced EMT
phenotype. The downstream target of TET3 was further identified. Finally, the
relationships of TET3 expression to clinic-pathological parameters of ovarian
cancer were investigated with a tissue microarray using immunohistochemistry.
RESULTS: TET3 was downregulated during TGF-?1-initiatd epithelial-mesenchymal
transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3
reversed TGF-?1-induced EMT phenotypes including the expression pattern of
molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and
invasive capabilities of ovarian cancer cells. miR-30d was identified as a
downstream target of TET3, and TET3 overexpression resumed the demethylation
status in the promoter region of miR-30d precursor gene, resulting in restoration
of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous
study) level in TGF-?1-induced EMT. We further found that TET3 expression was
decreased in ovarian cancer tissues, especially in serous ovarian cancers. The
overall positivity of TET3 was inversely correlated with the grade of
differentiation status of ovarian cancer. CONCLUSION: Our results revealed that
TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor
gene promoter to block TGF-?1-induced EMT.