Expression Of MicroRNA And Its Target Gene Analysis In Peripheral T-cell Lymphoma, Not Otherwise Specified

Background and ObjectivePeripheral T-cell lymphoma，not otherwise specified (PTCL-NOS) origins from matureT-cells, which is a type of rare and heterogeneous non-Hodgkin’s lymphoma (NHL) intissue morphology, immune phenotyping, and genetying or clinical features. This tumoris characterized by widespread dissemination, aggressive behaviour and a very pooroutcome. At present, its pathogenesis is not clear, and so its diagnosis and treatment aredifficult. microRNAs(miRNAs)are18-25-nucleotide non-coding RNAs that have highlyconservative in evolution. The miRNAs regulate gene expression in the transcriptionlevel, which bind to specific mRNA3′UTR leading to their degradation and/ortranslational blocking. In recent years, many studies show that miRNAs are closelyassociated with hematopoietic and lymphoid tumors. But the study about the expressionof microRNA in PTCL-NOS has not been reported yet. Therefore, the purpose of thisstudy was to investigate the expression profile of miRNAs in PTCL-NOS and to explorethe molecular characteristics.MethodsTaqMan low density array and qRT–PCR were used to assess the expression level of754miRNAs in6cases of PTCL-NOS and3cases of reactive lymphoid hyperplasia ascontrol. Real-time PCR was used to validate the miRNA expression profiling in28cases of PTCL-NOS. Bioinformatics tools were used for predicting target genes, the gene ontology (GO) analysis and pathway analysis were also carried out in this study.Results1. Histopathologic characteristics and immunopheniotyping.Among the28cases of PTCL-NOS,15cases were male, and13cases were female, withmedian age of62years (range12~80years); they presented as nodal or extranodaldiseases in21/28and7/28of the cases, respectively; the tumors showed effacement ofthe normal architecture with diffuse infiltration of polymorphous lymphoid cells. Thecytological spectrum was extremely broad, and usually they showed a predominance ofmedium-size or large cells with irregularly shape nuclei, hyperchromatic or vesicularnuclei and prominent nucleoli. Neoplastic cells were mixed with reactive elements, suchas follicular dendritic cells, Reed-Sternberg-like cells, eosinophils, small lymphocytes,plasma cells, large B-cell and some angiogenesis (branching high endothelial venules)in tumor stroma; Immunopheniotyping showed that28cases expressed CD3in differentdegree, the proliferating index of tumor cells was usually high with Ki-67positiveratesof about10-90%.2. miRNA array analysis and qRT-PCR validationMiRNA array results showed that eight miRNAs were significantly different betweenPTCL-NOS and benign reactive lymphoid hyperplasia. The expression of miR-886-3p，miR-511，miR-1291，miR-572，miR-27a-3p，miR-25-3p and miR-886-5p wassignificantly up-regulated in PTCL-NOS while miR-182-5p was significantlydown-regulated (P<0.05). The qRT-PCR results of three miRNA s(miR-1291，miR-511and miR-572) showed that these miRNAs were over-expressed in PTCL-NOS, in whichmiR-572expression had significantly statistical significance(P<0.05). 3. Bioinformatics analysisTarget genes prediction showed that1646candidate genes involved in the pathogenesisand progression of PTCL-NOS；Gene Ontology(GO)and Pathway analysis found thesegenes significantly focused on63GO terms and61pathways. GO analyses resultsshowed that genes function was mainly enriched in organ development, metabolism,cell division, differentiation, and intracellular signal transduction, protein synthesis, etc.Pathway-analysis results showed that the gene functions involved in many signalingpathways, such as MAPK signaling pathway, cancer pathways, VEGF signalingpathway, Wnt signaling pathway, TGF-β signaling pathways, cell adhesion molecules,and so on.Conclusions1. Eight miRNAs are aberrantly expressed in PTCL-NOS, in which seven miRNAs(miR-886-3p，miR-511，miR-1291，miR-572，miR-27a-3p，miR-25-3p and miR-886-5p)are up-regulated and one (miR-182-5p) is down-regulated, which could be used in thedifferential diagnosis between PTCL-NOS and reactive lymphoid hyperplasis. ThesemiRNAs might be involved in the molecular pathogenesis of PTCL-NOS, and theirclinical implication needs to be clarified.2. The abnormal expression of the miRNAs are involved in a variety of complex targetgenes and multiple signaling pathways in PTCL-NOS, which provide some referencedata for further function research of those miRNAs.