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.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive B-cell lymphoma
Among the diffuse large B-cell lymphoma (DLBCL), we observed several for validation using Reverse transcription quantitative PCR (RT-qPCR)
We found a significant increase in the precursor miRNA processing efficiency in de novo DLBCLs as compared with lymph nodes (LN) and transformed DLBCLs
Summary
DLBCL), whereas a subset is transformed from a previous indolent lymphoma. This disease is very heterogeneous with significantly different clinical outcomes,[1,2,3] and advanced knowledge of the biology of DLBCL is crucial for future advances in treatment management. While there has been progress in understanding the molecular genetics of these tumors,[1,2,4] the detailed network of events leading to DLBCL development and progression has yet to be elucidated. We aimed to determine the role of microRNAs (miRNAs) and their processing factors in DLBCL development, as well as their clinical implications
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
