摘要：Enhancer DNA methylation and expression of
MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the
MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7–50.0%) than normal plasma cells (37.5–75.0%) (P = 0.007), which was negatively correlated with qPCR-measured
MYBPHL expression. In RPMI-8226 and WL-2 cells, bearing the highest CpG1 methylation, 5-azadC caused enhancer demethylation and expression of
MYBPHL. In primary samples, higher CpG1 methylation was associated with lower
MYBPHL expression. By luciferase assay, luciferase activity was enhanced by
MYBPHL enhancer compared with empty vector control, but reduced by site-directed mutagenesis of each CpG. RNA-seq data of newly diagnosed MM patients showed that
MYBPHL expression was associated with t(11;14). MOLP-8 cells carrying t(11;14) express the highest levels of
MYBPHL, and its knockdown reduced cellular proliferation and increased cell death. Herein, as a proof-of-concept, our data demonstrated that the
MYBPHL enhancer, particularly CpG1, was hypomethylated and associated with increased
MYBPHL expression in MM, which was implicated in myelomagenesis.
