PAX5 Targets TFII-I And IRF4 To Promote Multiple Myeloma Cell Growth

As a member of Pax (Paired box) transcription factor family, PAX5 is the only one who distributed in hematopoietic cells. It decides B cell growth and differentiation by repressing B cell lineage inappropriate genes and simultaneously activating B lineage specific genes. Thus PAX5 can both represses and activates a subset of genes transcription. Studies have shown that PAX5 is presented during B cell development and differentiation from pro-B to mature B cells, and its expression is shutted down in terminally differentiated B cells.Multiple myeloma (MM) is still an incurable disease that is characterized by both mature B cell and plasma cell identities. Constitutive expression of PAX5 has been detected in both clinal samples and cell lines of MM, which has been implicated in promoting MM growth.To elucidate the roles and mechanisms of PAX5 in MM, a MM cell line IM9 was employed and stably transfected with the plasmid containing shRNA specific targeting PAX5 was established. By screening the potential PAX5 targeted genes, we discovered that PAX5 regulates TFII-I transcription through directly binding to a PAX5 binding site within TFII-I promotor region and promotes IM9 cell growth.Moreover, IRF4, another important oncogene that implicated in MM, was also found to be induced by PAX5 through transcriptional regulation and involved in promoting MM cell growth. Combination of inhibition of both PAX5 and IRF4 by siRNA showed a maximal inhibitory effect of MM cell growth. Furthermore, knockdown PAX5 lead to significant increase of drug sensitivity to Bortezomib in MM cells, that underscores the anti-apoptosis role of PAX5 in MM.