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MicroRNA profiling in ocular adnexal extranodal marginal zone lymphoma and diffuse large B‐cell lymphoma
Author(s) -
RASMUSSEN P,
HOTHER C,
JOSHI T,
REKER D,
RALFKAER U,
WORKMAN C,
RALFKAER E,
GRONAEK K,
HEEGAARD S
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.4666.x
Subject(s) - marginal zone , lymphoma , pathology , diffuse large b cell lymphoma , medicine , b cell , immunology , antibody
Purpose To investigate changes in microRNA (miR) expression in ocular adnexal extranodal marginal zone lymphoma (EMZL) and diffuse large B‐cell lymphoma (DLBCL), and to perform a pathway analysis of differentially expressed miRs. Methods Global miR expression profiling was performed using miRCURYTM LNA miR‐arrays, v. 11.0, (Exiqon) on formalin‐fixed paraffin‐embedded tissue from 18 ocular adnexal EMZLs and 25 DLBCLs. The result of microarray was confirmed using quantitative real time (RT)‐PCR. Predicted and validated targets of the significantly differentially expressed miRs were obtained from MiR‐walk. Transcription factor (TF)‐miR interactions were obtained from the TransmiR database. Results The microarray results revealed two up‐regulated and 41 down‐regulated miRs in the DLBCLs compared to the EMZLs. Further, the differentially expressed miRs separated EMZLs and DLBCLs into two distinct entities using a supervised clustering analysis. These findings were confirmed by quantitative RT‐PCR. Five of the down‐regulated miRs (let‐7g, miR‐26a, miR‐29a, miR‐29c and miR‐221) were identified to be regulated negatively by MYC. A small set of miRs (let‐7g, miR‐199a‐5, miR‐26a, miR‐27a* and miR‐342‐3p) that regulate NFKB1 were all down‐regulated in the DLBCLs compared to the EMZL samples. Further, the NFKB1 regulated miRs (miR‐29a/b/c and miR‐125b) were down‐regulated significantly in the DLBCLs compared with the EMZLs (log2 fold‐changes: miR‐29a/b/c < ‐1.9 and ‐1.1 for miR‐125b). Conclusion We demonstrated that fundamental differences in miR expression exist between ocular adnexal EMZLs and DLBCLs, mainly due to differences in MYC and NF‐kB regulatory pathways.