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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
- Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon
- J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016
- DOI: https://doi.org/10.4132/jptm.2016.06.06
- 9,477 View
- 173 Download
- 26 Web of Science
- 23 Crossref
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Abstract
PDF - 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. -
Citations
Citations to this article as recorded by
- HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives
Majid Nazari, Emad Babakhanzadeh, Arghavan Mollazadeh, Mohadese Ahmadzade, Elham Mohammadi Soleimani, Elnaz Hajimaqsoudi
Cancer Cell International.2024;[Epub] CrossRef - Long noncoding RNAs (lncRNAs) in human lymphomas
Ali Gholami, Khosro Farhadi, Fatemeh Sayyadipour, Masoud Soleimani, Fakhredin Saba
Genes & Diseases.2022; 9(4): 900. CrossRef - Long noncoding RNAs (lncRNAs) in HIV-mediated carcinogenesis: Role in cell homeostasis, cell survival processes and drug resistance
Lilian Makgoo, Salerwe Mosebi, Zukile Mbita
Non-coding RNA Research.2022; 7(3): 184. CrossRef - Biomedical impact of the expression of HOX locus-associated LncRNAs HOTAIR and HOTTIP in diffuse large B cell lymphoma
Mona Salah Eldin Habieb, Suzy Fawzy Goher, Abd-Elmonem Abd-Elkader El-Torgman, Ibrahim El Tantawy El Sayed, Najlaa Zanati Ali Abd-Elfattah
Human Gene.2022; 34: 201112. CrossRef - Mechanism of LncHOTAIR Regulating Proliferation, Apoptosis, and Autophagy of Lymphoma Cells through hsa-miR-6511b-5p/ATG7 Axis
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Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. CrossRef -
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Experimental Hematology & Oncology.2021;[Epub] CrossRef - Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness
Mahmoud A. Senousy, Aya M. El-Abd, Raafat R. Abdel-Malek, Sherine M. Rizk
Scientific Reports.2021;[Epub] CrossRef - An immunotherapeutic approach to decipher the role of long non-coding RNAs in cancer progression, resistance and epigenetic regulation of immune cells
Krishnapriya M. Varier, Hemavathi Dhandapani, Wuling Liu, Jialei Song, Chunlin Wang, Anling Hu, Yaacov Ben-David, Xiangchun Shen, Yanmei Li, Babu Gajendran
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef - Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression
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Oncology Letters.2021;[Epub] CrossRef - Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives
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APMIS.2020; 128(4): 308. CrossRef Long Noncoding RNAs in Diffuse Large B-Cell Lymphoma: Current Advances and Perspectives
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Xiao-Hui Zhang, Pin Hu, Yang-Qin Xie, Yong-Jun Kang, Min Li
Molecular and Cellular Biology.2019;[Epub] CrossRef - EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications
Boheng Li, Wee-Joo Chng
Journal of Hematology & Oncology.2019;[Epub] CrossRef - The prognostic impact of long noncoding RNA HOTAIR in leukemia and lymphoma: a meta-analysis
Yun Lin, Zhihong Fang, Zhijuan Lin, Zhifeng Li, Jintao Zhao, Yiming Luo, Bing Xu
Hematology.2018; 23(9): 600. CrossRef - Retracted: Downregulation of Long Noncoding RNA HOTAIR and EZH2 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Breast Cancer Cells
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Cancer Biotherapy and Radiopharmaceuticals.2018; 33(6): 241. CrossRef - Long Non-Coding RNAs Guide the Fine-Tuning of Gene Regulation in B-Cell Development and Malignancy
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International Journal of Molecular Sciences.2018; 19(9): 2475. CrossRef - HOTAIR, a long noncoding RNA, is a marker of abnormal cell cycle regulation in lung cancer
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Cancer Science.2018; 109(9): 2717. CrossRef - The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors
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Laboratory Investigation.2017; 97(10): 1142. CrossRef - Emerging roles for long noncoding RNAs in B-cell development and malignancy
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Critical Reviews in Oncology/Hematology.2017; 120: 77. CrossRef
- HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives
- Gene Expressions of Mouse Submandibular Gland during the Developmental Stage and Their Antisense Inhibition in Organ Culture.
- Yeon Sook Kim, Suk Keun Lee, Je G Chi
- Korean J Pathol. 2000;34(6):395-412.
- 1,689 View
- 11 Download
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Abstract
PDF
- This study is aimed to observe the expressions of different genes, including the extracellular matrix proteins, growth factors, and transcription factors during different developmental stages of mouse submandibular gland. Reverse transcription-polymerase chain reaction (RT-PCR) and the antisense inhibition in organ culture system were performed using mouse embryos and newborns. Total 140 mouse embryos (E14(80), E15(20), E16(20), E18(20)) and 30 newborn mice (D2(10), D3(10), D6(10)) obtained from 60 pregnant mice and 3 adult mice (3 weeks old) were used for the cDNA production and the salivary gland organ culture. Syndecan, perlecan, laminin alpha1 chain, TGF beta1, beta 3, and sonic hedgehog mRNAs were expressed in the early stage (E14~E16) of the submandibular gland development, whereas transglutaminase C (TGase C), E-cadherin, epimorphin, laminin beta2 and gamma1 chains, and HGF mRNAs were expressed in the middle and late stages (E16~E18, D2~D6). Antisense inhibition of different genes in the organ culture of E14 mouse embryos of submandibular gland showed specific growth retardation in the development of ductal and acinar cells. Especially, the antisense inhibition of perlecan, E-cadherin, laminin alpha1 chain, laminin beta2 chain, and syndecan mRNA arrested the growth of ductal and acinar cells. While the antisense inhibition of integrin beta5 greatly affected the acinar cell differentiation and also produced cystic dilatation of salivary ducts, the antisense inhibition of fibronectin showed aberrant growth of ectomesenchymal tissues of the mouse submandibular gland.
- The Effect of Antibody and Gene Therapy for Transforming Growth Factor- 1 on Scar Formation.
- Jun Hyung Kim, Ki Hwan Han, Jong Duck Ahn, In Kyu Lee, Eun Joo Kim, Mee Yul Hwang, Kwan Kyu Park
- Korean J Pathol. 2001;35(5):424-432.
- 1,640 View
- 13 Download
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Abstract
PDF
- BACKGROUND
Transforming growth factor (TGF)- has a large variety of biological functions, including the modulation of inflammation and the immune system, and is presumed to play important roles in repairing wounds and reducing scarring. The objective of this study is to examine the effects of TGF-1 on healing wounds and reducing scarring. We have also analysed the ability of the hemagglutinating virus of Japan (HVJ) liposome mediated antisense oligodeoxynucleotides (ODNs) to specifically inhibit wound-induced expressions of TGF-1 proteins and mRNA in the rat skin.
METHODS
Skin wounds were created on the backs of 80 anesthetized rats. The first group of wounds, as the controls, was unmanipulated. The second group of wounds, as positive controls or an excessive scarring model, was injected with TGF-1 subcutaneously. The third group of wounds was injected with anti-TGF-1 antibody subcutaneously. The fourth group of wounds was injected with HVJ liposome mediated antisense ODNs for TGF-1 subcutaneously. The wounds of all groups were bisected and analysed histologically 5, 10, 15, 30, and 50 days after the wounds were made.
RESULTS
All control wounds (TGF-1 or no injection) healed with scarring, whereas the wounds treated with the antibody or antisense ODNs healed with less scar formation compared to the control group. The wounds treated with the antibody or antisense ODNs had fewer macrophages, less collagen and fibronectin contents than the other wounds. Northern blotting and in situ hybridization analysis showed that wound sites treated with HVJ liposome mediated antisense ODNs for TGF-1 exhibited decreased levels of TGF-1 mRNA after injury.
CONCLUSIONS
These findings suggest an important new approach to controlling scarring in normal wound healing, complementing the practice of adding exogenous growth factors to chronic wounds in the attempt to inhibit collagen deposition.
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