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Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors

 Na Keum Lee  ;  Jung Hwa Lee  ;  Won Kyu Kim  ;  Seongju Yun  ;  Young Hoon Youn  ;  Chan Hyuk Park  ;  Yun Young Choi  ;  Hogeun Kim  ;  Sang Kil Lee 
 ONCOTARGET, Vol.7(46) : 75307-75318, 2016 
Journal Title
Issue Date
Apoptosis/genetics ; Azacitidine/pharmacology ; Cadherins/genetics* ; Cell Cycle Checkpoints/genetics ; Cell Line, Tumor ; Cell Proliferation ; DNA Methylation* ; Disease Progression ; Epigenesis, Genetic*/drug effects ; Gastrointestinal Stromal Tumors/genetics* ; Gastrointestinal Stromal Tumors/pathology* ; Gene Expression Regulation, Neoplastic* ; Gene Silencing ; Humans ; Promoter Regions, Genetic* ; RNA, Long Noncoding/genetics*
HOTAIR ; PCDH10 ; gastrointestinal stromal tumor
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Kyu(김원규)
Kim, Hogeun(김호근)
Youn, Young Hoon(윤영훈) ORCID logo https://orcid.org/0000-0002-0071-229X
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
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