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, SangKil Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)75307-75318
Number of pages12
JournalOncotarget
Volume7
Issue number46
DOIs
Publication statusPublished - 2016 Jan 1

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Gastrointestinal Stromal Tumors
Methylation
Long Noncoding RNA
Stromal Cells
Genes
Disease Progression
Cell Cycle
Apoptosis
Neoplasm Metastasis
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Lee, Na Keum ; Lee, Jung Hwa ; Kim, Won Kyu ; Yun, Seongju ; Youn, Young Hoon ; Park, Chan Hyuk ; Choi, Yun Young ; Kim, Hogeun ; Lee, SangKil. / Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors. In: Oncotarget. 2016 ; Vol. 7, No. 46. pp. 75307-75318.
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Lee, NK, Lee, JH, Kim, WK, Yun, S, Youn, YH, Park, CH, Choi, YY, Kim, H & Lee, S 2016, 'Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors', Oncotarget, vol. 7, no. 46, pp. 75307-75318. https://doi.org/10.18632/oncotarget.12171

Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors. / Lee, Na Keum; Lee, Jung Hwa; Kim, Won Kyu; Yun, Seongju; Youn, Young Hoon; Park, Chan Hyuk; Choi, Yun Young; Kim, Hogeun; Lee, SangKil.

In: Oncotarget, Vol. 7, No. 46, 01.01.2016, p. 75307-75318.

Research output: Contribution to journalArticle

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AU - Lee, Na Keum

AU - Lee, Jung Hwa

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AU - Kim, Hogeun

AU - Lee, SangKil

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