Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

Abstract

Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL.

Identification of novel microRNA signatures linked to acquired aplastic anemia

“…MiR-126-3p and miR-145-4p are known to be down-regulated in B-cell malignancies, such as chronic lymphocytic leukemia and diffuse large B-cell lymphoma, respectively. 49,50 Moreover, autoantibodies are frequently detected in patients with AA. 51,52 Perhaps dysregulations of B cells is related to aberrant B-cell activation.…”

Molecular genetics related to non-Hodgkin lymphoma

“…Although overexpression of MYC is driven by an immunoglobulin gene enhancer generally associated with BL, recurrent genetic abnormalities apart from MYC are reported. Abnormalities of chromosomes 1, 6, 7, 13, 17 and 22 are reported in pediatric BL [23][24]. In studies of BL samples, cytogenetic abnormalities have been reported.…”

MicroRNAs in diffuse large B-cell lymphoma

“…Previous studies have confirmed that miRs are involved in the pathogenesis of DLBCL (17,18). In 2009, Li et al (19) used a miR chip method to analyze the expression of pathological tissues from 59 patients with DLBCL and 26 types of existing DLBCL cell lines.…”