Ruonan Xu, Ying Fang, Chunmei Hou and Bing Zhai contributed equally to this work
Both multiple myeloma (MM) and systemic lupus erythematosus (SLE) are associated with abnormal production of plasma cells, although their pathological mechanism of each disease is different. The main characteristic of both diseases is uncontrolled differentiation of B cells into plasmablast/plasma cells. Despite continuous research on prognostic factors and the introduction of new agents for MM and SLE, treatments still do not exist for controlling plasmablast/plasma cells. Thus, it is necessary to identify novel therapeutic targets of plasmablast/plasma cells. Because of its plasmablast-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to test the effect of a novel therapeutic agent (BC094916 overexpression) on plasmablast/plasma cells.
We first determined gene expression profiles of plasma cells using Affymetrix microarrays and RNA-sequencing. The effect of BC094916 on SP 2/0 cell proliferation, cell cycle, and apoptosis was determined by CCK8 and fluorescence-activated cell sorting. The SP 2/0 xenograft mouse model was used to assess the impact of BC094916 on tumor progression. The luciferase reporter system was used to evaluate the effect of BC094916 on Creb1 and Bcl2 transcription.
We found that BC094916 mRNA was decreased in plasma cells. The mouse myeloma cell line SP 2/0 expressed low levels of BC094916 mRNA, whereas BC094916 overexpression suppressed SP 2/0 cell proliferation by inducing apoptosis. BC094916 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. We also found that BC094916 mediate apoptosis by suppressing transcription of the Creb1 and Bcl2 genes, which promote the transcription of eukaryotic translation initiation and elongation factor genes.
BC094916 overexpression suppressed Creb1 and Bcl2 transcription to induce cell apoptosis, which suppressed SP 2/0 proliferation and xenograft tumor progression. Thus, BC094916 overexpression may be a potential therapeutic agent for treatment of MM and autoimmune diseases such as SLE.