Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection

Abstract

The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases. We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV þ SMZL; 8 HCV À SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P ¼ 0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

“…Thus, the miRNome of splenic marginal zone lymphoma determined in the present study suggests that this tumor is a neoplastic expansion of memory B cells, similar to what our group has observed for nodal marginal zone lymphoma. 16 Our findings confirm the increased expression of miR-155 in splenic marginal zone lymphoma 15 and other lymphoid neoplasias. [27][28][29]33 MiR-155 is involved in the development of different B-cell differentiation stages 34 and helps regulate essential immune functions.…”

“…We found previously described miRNAs forming part of the splenic marginal zone lymphoma signature that were deregulated in this lymphoma type, such as the overexpressed miR-21, miR-34a and miR-155, the repressed miR-139, 15 and miRNAs deregulated in other tumors, such as miR-21, 27-30 miR-34a 31 and miR-193b. 32 The most significant miRNAs observed in the splenic marginal zone lymphoma signature were miR-155, miR-34a, miR193b, miR-21, miR-377, miR-376a, miR-27b and miR-145.…”

“…12,13 The miRNA profile of splenic marginal zone lymphoma has been investigated by several groups, who have obtained interesting results related with 7q loss, hepatitis C virus presence or with normal spleen. 4,5,14,15 Nevertheless, the miRNA changes in splenic marginal zone lymphoma are yet to be comprehensively described. We aimed to carry out an integrated genomics study to improve our understanding of the molecular mechanisms involved in the pathogenesis of splenic marginal zone lymphoma, and to suggest new targets, genes and miRNAs, with diagnostic and therapeutic potential.…”

Human and Viral microRNA Expression in Sjögren Syndrome

“…Similarly to miRNA-146a, miRNA-155 has also been implicated in a variety of pathologies 8,9,10 . However, in the case of SS and in relation to the viral differentially expressed microRNA reported in this article, the relation of miRNA-155 to Epstein-Barr virus infection (EBV) 11,12 and the association of this microRNA to lymphomas deserve further evaluation 13,14,15 .…”

The Diagnostic and Prognostic Impact of Serum miRNA-21 in a Sample of Hepatitis C/None Hepatitis Diffuse Large B Cell Lymphoma Egyptian Patients

“…In addition to our knowledge, there are no existing data up to date on the expression of miRNA-21 in HCV related DLBCL. Most of the studies conducted were performed on splenic marginal zone lymphoma (SMZL) patients [17]. Thus in this study we aimed to identify the expression and the prognostic implications of miRNA-21 in DLBCL cases and to evaluate its differential expression in GCB and ABC sub-types and its impact on response to chemotherapy as well as survival in each sub-type.…”