Aneuploidy and overexpression of hsa-miR-155-5p (miR-155) characterize most solid and
hematological malignancies. We recently demonstrated that miR-155 sustains
aneuploidy at early stages of in vitro cellular transformation. During in vitro transformation of normal human fibroblast, upregulation of miR-155 downregulates spindle checkpoint
proteins as the mitotic checkpoint
serine/threonine kinase budding uninhibited by
benzimidazoles 1 (BUB1), the
centromere protein F (CENPF) and the zw10 kinetochore
protein (ZW10), compromising the chromosome alignment at the metaphase plate and leading to
aneuploidy in daughter cells. Here we show that the
heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to the polymorphic marker D2S1888 at the
3'UTR of BUB1 gene, impairs the miR-155 targeting, and restores BUB1 expression in
chronic lymphocytic leukemia. This mechanism occurs at advanced passages of cell transformation and allows the expansion of more favorable clones. Our findings have revealed, at least in part, the molecular mechanisms behind the chromosomal stabilization of cell lines and the concept that, to survive,
tumor cells cannot continuously change their genetic heritage but need to stabilize the most suitable karyotype.