Article: Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma

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TitleDysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma
AuthorsNg, SB1
Yan, J4
Huang, G4
Selvarajan, V1
Tay, JLS4
Lin, B4
Bi, C4
Tan, J4
Kwong, YL2
Shimizu, N5
Aozasa, K3
Chng, WJ4 6
Issue Date2011
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
CitationBlood, 2011, v. 118 n. 18, p. 4919-4929 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2011-07-364224
AbstractWe performed a comprehensive genomewide miRNA expression profiling of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed paraffin-embedded tissue (n ∇ 30) and NK cell lines (n ∇ 6) compared with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Compared with normal NK cells, differentially expressed miRNAs in NKTL are predominantly downregulated. Re-expression of downregulated miRNAs, such as miR-101, miR- 26a, miR26b, miR-28-5, and miR-363, reduced the growth of the NK cell line and modulated the expression of their predicted target genes, suggesting the potential functional role of the deregulated miRNAs in the oncogenesis of NKTL. Taken together, the predicted targets whose expression is inversely correlated with the expression of deregulated miRNA in NKTL are significantly enriched for genes involved in cell cycle-related, p53, and MAPK signaling pathways. We also performed immunohistochemical validation for selected target proteins and found overexpression of MUM1, BLIMP1, and STMN1 in NKTL, and notably, a corresponding increase in MYC expression. Because MYC is known to cause repression of miRNA expression, it is possible that MYC activation in NKTL may contribute to the suppression of the miRNAs regulating MUM1, BLIMP1, and STMN1. © 2011 by The American Society of Hematology.
ISSN0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
DOIhttp://dx.doi.org/10.1182/blood-2011-07-364224
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorNg, SB
dc.contributor.authorYan, J
dc.contributor.authorHuang, G
dc.contributor.authorSelvarajan, V
dc.contributor.authorTay, JLS
dc.contributor.authorLin, B
dc.contributor.authorBi, C
dc.contributor.authorTan, J
dc.contributor.authorKwong, YL
dc.contributor.authorShimizu, N
dc.contributor.authorAozasa, K
dc.contributor.authorChng, WJ
dc.date.accessioned2012-09-05T05:31:05Z
dc.date.available2012-09-05T05:31:05Z
dc.date.issued2011
dc.description.abstractWe performed a comprehensive genomewide miRNA expression profiling of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed paraffin-embedded tissue (n ∇ 30) and NK cell lines (n ∇ 6) compared with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Compared with normal NK cells, differentially expressed miRNAs in NKTL are predominantly downregulated. Re-expression of downregulated miRNAs, such as miR-101, miR- 26a, miR26b, miR-28-5, and miR-363, reduced the growth of the NK cell line and modulated the expression of their predicted target genes, suggesting the potential functional role of the deregulated miRNAs in the oncogenesis of NKTL. Taken together, the predicted targets whose expression is inversely correlated with the expression of deregulated miRNA in NKTL are significantly enriched for genes involved in cell cycle-related, p53, and MAPK signaling pathways. We also performed immunohistochemical validation for selected target proteins and found overexpression of MUM1, BLIMP1, and STMN1 in NKTL, and notably, a corresponding increase in MYC expression. Because MYC is known to cause repression of miRNA expression, it is possible that MYC activation in NKTL may contribute to the suppression of the miRNAs regulating MUM1, BLIMP1, and STMN1. © 2011 by The American Society of Hematology.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationBlood, 2011, v. 118 n. 18, p. 4919-4929 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2011-07-364224
dc.identifier.citeulike10001569
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2011-07-364224
dc.identifier.epage4929
dc.identifier.issn0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
dc.identifier.issue18
dc.identifier.pmid21921041
dc.identifier.scopuseid_2-s2.0-80855128777
dc.identifier.spage4919
dc.identifier.urihttp://hdl.handle.net/10722/163413
dc.identifier.volume118
dc.languageeng
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
dc.publisher.placeUnited States
dc.relation.ispartofBlood
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshCaenorhabditis Elegans - Genetics
dc.subject.meshCell Line, Tumor
dc.subject.meshCluster Analysis
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation, Neoplastic - Physiology
dc.subject.meshHumans
dc.subject.meshKiller Cells, Natural - Metabolism - Pathology
dc.subject.meshLymphoma, Extranodal Nk-T-Cell - Diagnosis - Genetics - Metabolism - Therapy
dc.subject.meshMicrornas - Genetics - Metabolism
dc.subject.meshMicroarray Analysis
dc.subject.meshMolecular Targeted Therapy
dc.subject.meshPrognosis
dc.subject.meshSignal Transduction - Genetics - Physiology
dc.subject.meshTransfection
dc.titleDysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma
dc.typeArticle
Author Affiliations
  1. Yong Loo Lin School of Medicine
  2. Queen Mary Hospital Hong Kong
  3. Osaka University Faculty of Medicine
  4. National University of Singapore
  5. Tokyo Medical and Dental University
  6. National University Hospital, Singapore