Significance Of MicroRNA In Diffuse Large B-cell Lymphoma And Its Relation To Prognosis And Immunophenotyp

Background:While it is known that diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs (miRs) in the pathogenesis of DLBCLs.Methods:A retrospective cohort of106primary nodal DLBCL samples with varying clinicopathological characteristics were collected from the Department of Hematology of Shanxi Cancer Hospital and underwent treatment with the standard CHOP regimen. Immunohistochemical Envision methord was invited to detect the expression of CD3、 CD20、CD10、Bcl-6、MUM1in106cases of DLBCL. The DLBCL were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans’algorithm. MiR profiling was carried out using the Agilent Human miRNA Microarray16.0. Quantitative RT-PCR (qRT-PCR) was used to confirm the differences in the expression of miRs among DLBCL samples. Myc gene rearrangements were analyzed by interphase fluorescent in situ hybridization. Cell proliferation and apoptosis were quantitated by Cell Counting Kit-8and AnnexinV/7ADD staining, respectively. Overexpression of miRs was performed by lentiviral transduction, whereas shRNA knockdown of miRs was also performed using lentiviral transduction.Results:The median overall survival (OS) of DLBCL patients in this cohort was40.8months. MiR-146b-5p and miR-320d were expressed at lower levels in DLBCLs from patients with overall survival<40.8months than those from patients survived≥40.8months. Indeed, while low expression of miR-146b-5p was correlated with reduced progression-free survival (PFS), low expression of miR-320d was associated with decreases in both OS and PFS. Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels in DLBCLs with the Myc t(8;14) translocation. Functional studies demonstrated that overexpression of miR-146b-5p and miR-320d inhibited DLBCL cell proliferation, whearas knockdown of miR-146b-5p or miR-320d promoted proliferation of DLBCL cells.Conclusion:Low expression of miR-146b-5p or miR-320d identifies a subset of DLBCL patients who may have compromised responses to treatment with the CHOP regimen. This is associated with the inhibitory effect of these miRs on DLBCL cell proliferation.