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Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation

Authors
 Eun Ji Oh  ;  Soo Hee Kim  ;  Woo Ick Yang  ;  Young Hyeh Ko  ;  Sun Och Yoon 
Citation
 JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE, Vol.50(5) : 369-376, 2016 
Journal Title
 JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE 
ISSN
 2383-7837 
Issue Date
2016
Keywords
HOTAIR ; Histone H3trimethylation at lysine 27 ; Lymphoma, large B-cell, diffuse ; Polycomb repressive complex2 ; hox transcript antisense intergenic RNA
Abstract
BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs). METHODS: The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs. RESULTS: The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression. CONCLUSIONS: HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.
Files in This Item:
T201603792.pdf Download
DOI
10.4132/jptm.2016.06.06
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Hee(김수희)
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Oh, Eun Ji(오은지)
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152209
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