title: Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma.
abstract: We performed a comprehensive genome-wide 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 down-regulated. Re-expression of down-regulated 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.
authors.affiliation: Department of Pathology, National University Health System, Singapore.
authors.forename: Siok-Bian
authors.initials: SB
authors.lastname: Ng
authors.forename: Junli
authors.initials: J
authors.lastname: Yan
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Huang
authors.forename: Viknesvaran
authors.initials: V
authors.lastname: Selvarajan
authors.forename: Jim Liang-Seah
authors.initials: JL
authors.lastname: Tay
authors.forename: Baohong
authors.initials: B
authors.lastname: Lin
authors.forename: Chonglei
authors.initials: C
authors.lastname: Bi
authors.forename: Joy
authors.initials: J
authors.lastname: Tan
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Norio
authors.initials: N
authors.lastname: Shimizu
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D054391:Lymphoma, Extranodal NK-T-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D058990:Molecular Targeted Therapy; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: D035683:MicroRNAs