MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type
2018
Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for
BCL6. However, details about the interaction between MEF2B and
BCL6during expression, as well as the relationship of MEF2B to the expression of other
germinal center(GC) markers, have not yet been fully explained. Using
germinal center B-cell-like diffuse large B-cell lymphoma(GC-DLBCL) and activated B-cell
diffuse large B-cell lymphoma(ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with
BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the
BCL6transcriptional complex was performed using
electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of
BCL6, CD10, and ERK phosphorylation. Analysis of
BCL6transcription factors in nuclear extracts of
MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and
BCL6proteins in the formation of the
BCL6gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in
tissue microarray, as indicated via immunohistochemistry (Visco–Young algorithm). Our findings indicate that MEF2B is an essential component of the
BCL6gene transcriptional complex for the regulation of DLBCL growth via the promotion of
BCL6expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with
BCL6and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.
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