Research Papers:

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 and Sang Kil Lee _

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Oncotarget. 2016; 7:75307-75318. https://doi.org/10.18632/oncotarget.12171

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Na Keum Lee1, Jung Hwa Lee1, Won Kyu Kim2, Seongju Yun2, Young Hoon Youn1, Chan Hyuk Park1, Yun Young Choi1, Hogeun Kim2, Sang Kil Lee1

1Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea

2Department of pathology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea

Correspondence to:

Sang Kil Lee, email: [email protected]

Keywords: PCDH10, HOTAIR, gastrointestinal stromal tumor

Received: January 26, 2016     Accepted: September 12, 2016     Published: September 21, 2016


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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