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2016 ; 7
(46
): 75307-75318
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Promoter methylation of PCDH10 by HOTAIR regulates the progression of
gastrointestinal stromal tumors
#MMPMID27659532
Lee NK
; Lee JH
; Kim WK
; Yun S
; Youn YH
; Park CH
; Choi YY
; Kim H
; Lee SK
Oncotarget
2016[Nov]; 7
(46
): 75307-75318
PMID27659532
show ga
HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation
and metastasis by interacting with the PRC2 complex and the modulation of its
target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is
remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and
promotion of GISTs. The expression of HOTAIR was found to be higher in surgically
resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using
GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was
associated with cell cycle progression, and controlled the invasion and migration
of GIST cells. Using a gene expression microarray and lists of HOTAIR-associated
candidate genes, we suggested that protocadherin 10 (PCDH10) is a key molecule.
PCDH10 expression was significantly decreased in GIST-T1 and GIST882 cells,
possibly as a consequence of hypermethylation. We observed that HOTAIR induced
PCDH10 methylation in a SUZ12-dependent manner. In this study, we found that the
malignant character of GISTs was initiated and amplified by PCDH10 in a process
regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be
useful markers of disease progression and therapeutic targets.