Evaluation of Methylation at Promoter Regions of Long Non-coding RNAs in Patients with Acute Lymphoblastic Leukemia

被引:3
作者
Mousavi, Zohreh [1 ]
Ghorbian, Saeid [1 ]
Rezamand, Azim [2 ]
Roshangar, Leyla [3 ]
Jafari, Behboud [4 ]
机构
[1] Islamic Azad Univ, Ahar Branch, Dept Mol Genet, Ahar, Iran
[2] Tabriz Univ Med Sci, Pediat Hlth Res Ctr, Tabriz, Iran
[3] Tabriz Univ Med Sci, Stem Cell Res Ctr, Tabriz, Iran
[4] Islamic Azad Univ, Ahar Branch, Dept Microbiol, Ahar, Iran
关键词
Acute lymphoblastic leukemia; Long non-coding RNA; Methylation; Oncogenesis; ABERRANT DNA METHYLATION;
D O I
10.34172/PS.2021.18
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200 nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups. Methods: In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium hisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were evaluated using methylation specific-high resolution melting (MS-HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests. Results: The methylation levels of all studied lncRNAs including RP11-137H 2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were significantly increased (p<0.05). ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers. Conclusion: This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.
引用
收藏
页码:552 / 559
页数:8
相关论文
共 29 条
[1]  
[Anonymous], SEER Cancer Statistics Review, 1975-2004
[2]   Epigenetic regulation of hematopoietic stem cell aging [J].
Beerman, Isabel ;
Rossi, Derrick J. .
EXPERIMENTAL CELL RESEARCH, 2014, 329 (02) :192-199
[3]   DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction [J].
Broeske, Ann-Marie ;
Vockentanz, Lena ;
Kharazi, Shabnam ;
Huska, Matthew R. ;
Mancini, Elena ;
Scheller, Marina ;
Kuhl, Christiane ;
Enns, Andreas ;
Prinz, Marco ;
Jaenisch, Rudolf ;
Nerlov, Claus ;
Leutz, Achim ;
Andrade-Navarro, Miguel A. ;
Jacobsen, Sten Eirik W. ;
Rosenbauer, Frank .
NATURE GENETICS, 2009, 41 (11) :1207-1215
[4]   The hematopoietic stem cell niche in homeostasis and disease [J].
Calvi, Laura M. ;
Link, Daniel C. .
BLOOD, 2015, 126 (22) :2443-2451
[5]   Hematopoietic Stem Cell Development: An Epigenetic Journey [J].
Cullen, Sean M. ;
Mayle, Allison ;
Rossi, Lara ;
Goodell, Margaret A. .
STEM CELLS IN DEVELOPMENT AND DISEASE, 2014, 107 :39-75
[6]  
Navarrete-Meneses MD, 2017, B MED HOSP INFANT M, V74, P243, DOI 10.1016/j.bmhimx.2017.02.005
[7]   DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia [J].
Figueroa, Maria E. ;
Lugthart, Sanne ;
Li, Yushan ;
Erpelinck-Verschueren, Claudia ;
Deng, Xutao ;
Christos, Paul J. ;
Schifano, Elizabeth ;
Booth, James ;
van Putten, Wim ;
Skrabanek, Lucy ;
Campagne, Fabien ;
Mazumdar, Madhu ;
Greally, John M. ;
Valk, Peter J. M. ;
Lowenberg, Bob ;
Delwel, Ruud ;
Melnick, Ari .
CANCER CELL, 2010, 17 (01) :13-27
[8]   Epigenetics of Acute Lymphocytic Leukemia [J].
Garcia-Manero, Guillermo ;
Yang, Hui ;
Kuang, Shao-Qing ;
O'Brien, Susan ;
Thomas, Deborah ;
Kantarjian, Hogop .
SEMINARS IN HEMATOLOGY, 2009, 46 (01) :24-32
[9]   LncRNAs downregulated in childhood acute lymphoblastic leukemia modulate apoptosis, cell migration, and DNA damage response [J].
Gioia, Romain ;
Drouin, Simon ;
Ouimet, Manon ;
Caron, Maxime ;
St-Onge, Pascal ;
Richer, Chantal ;
Sinnett, Daniel .
ONCOTARGET, 2017, 8 (46) :80645-80650
[10]   Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms [J].
Hernandez, Antonio F. ;
Menendez, Pablo .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (04)