title: Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors.
abstract: 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.
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Na Keum
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Won Kyu
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Seongju
authors.initials: S
authors.lastname: Yun
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Youn
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Chan Hyuk
authors.initials: CH
authors.lastname: Park
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Yun Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of Pathology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Hogeun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea.
authors.forename: Sang Kil
authors.initials: SK
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001374:Azacitidine / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000187:drug effects; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D015820:Cadherins; C561566:HOTAIR long untranslated RNA, human; C438603:PCDH10 protein, human; D000091363:Protocadherins; D062085:RNA, Long Noncoding; D001374:Azacitidine
keywords: HOTAIR; PCDH10; gastrointestinal stromal tumor