Abstract
Background: The transcription factor MYC regulates several biological cellular processes, and its target gene network comprises approximately 15% of all human genes, including microRNAs (miRNAs), that also contribute to MYC regulatory activity. Although miRNAs are emerging as key regulators of immune functions, the specific roles of miRNAs in the regulation/dysregulation of germinal centre B-cells and B-cell lymphomas are still being uncovered. The regulatory network that integrates MYC, target genes and miRNAs is a field of intense study, highlighting potential pathways to be explored in the context of future clinical approaches. Methods: The scientific literature that is indexed in PUBMED was consulted for publications involving MYC and miRNAs with validated bioinformatics analyses or experimental protocols. Additionally, seminal studies on germinal centre B-cell functions and lymphomagenesis were reported. Conclusions: This review summarizes the interactions between MYC and miRNAs through regulatory loops and circuits involving target genes in germinal centre B-cell lymphomas with MYC alterations. Moreover, we provide an overview of the understanding of the regulatory networks between MYC and miRNAs, highlighting the potential implication of this approach for the comprehension of germinal centre B-cell lymphoma pathogenesis. Therefore, circuits involving MYC, target genes and miRNAs provide novel insight into lymphomagenesis that could be useful for new improved therapeutic strategies.
Highlights
The proto-oncogene c-MYC (MYC) codifies a transcription factor (TF), namely, MYC, that regulates several seminal biological cellular processes
Based on the involvement of miRNAs in the regulation of B-cell development/function and in lymphomagenesis, we review the roles of miRNAs in normal germinal centre (GC) reactions and focus on relevant feed-forward loops (FFLs) in the context of MYC-regulatory networks in GC-derived B-cell lymphomas
Cells have from features the light resembling zone (LZ); and cell-like (ABC)is related to B-cell lymphoma cellsactivated from theB light zone (LZ); diffuse large B-cell lymphoma (DLBCL)
Summary
The proto-oncogene c-MYC (MYC) codifies a transcription factor (TF), namely, MYC, that regulates several seminal biological cellular processes. In addition to regulating the transcription of mRNAs, MYC regulates the expression of microRNAs (miRNAs) by binding to specific DNA elements in the vicinity of their promoters [12]. MiRNAs are small non-coding RNAs (20–23 nucleotides in length), which bind to the 30 -UTRs of target mRNAs and regulate posttranscriptional expression by either triggering translational repression. MYC signalling pathways involving miRNAs have been associated with several relevant biological processes, such as proliferation, apoptosis, cell cycle progression, angiogenesis, and metabolic reprogramming [18]. FFLs indicates a complex MYC-regulatory network where MYC, as a TF, binds to the promoters of target genes via the canonical E-box sequence CACGTG, as well as to non-canonical DNA sequences, including CATGTG [21]. Based on the involvement of miRNAs in the regulation of B-cell development/function and in lymphomagenesis, we review the roles of miRNAs in normal germinal centre (GC) reactions and focus on relevant FFLs in the context of MYC-regulatory networks in GC-derived B-cell lymphomas
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