Abstract:
Background: As a common and incurable cancer originating from plasma cells, multiple myeloma (MM) represents 10% of hematological cancers. Most cancer-related genes involved in MM development are currently unknown. Deletions in chromosome 8p23.1, harboring multiple candidate tumor suppressor genes, are observed in MM tumor samples. SOX7, a transcription factor located in 8p23.1, was reported to be silenced in many cancer types; and its ectopic expression inhibited growth of different tumor types. Herein, we investigated whether SOX7 acts as a tumor supressor in MM or not.
Methods: In MM cell lines, SOX7 copy number, transcript, and protein expression analyses were investigated with qPCR, qRT-PCR, and western blot, respectively. SOX7 promoter methylation analysis of MM cell lines was performed through bisulfite sequencing. The SOX7 coding sequence was cloned into the PMIG retrovirus for transduction into two MM cell lines. GFP competition, cell cycle, and apoptosis assays were performed using these two MM cell lines with ectopic SOX7 expression.
Results: We observed monoallelic deletion of SOX7 in two out of five (40%) MM cell lines. Of significance, SOX7 promoter was hypermethylated in four out of five (80%) of the MM cell lines. Consistent with these observations, SOX7 was under-expressed in most MM cell lines. Ectopic expression of SOX7 with transduction in two SOX7 non-expressing MM cell lines resulted in progressive decrease in the percentage of GFP+ cells, suggesting that SOX7 expression exerts negative selection pressure on these MM cell lines. Cell cycle analysis showed increase of cells in G1 phase and decrease in S phase in two MM cell lines with no endogenous SOX7 expression. Similarly, apoptotic cell percentage was higher in SOX7 non- expressing MM cell lines with ectopic SOX7.
Conclusions: Based on our results, SOX7 is genetically and epigenetically inactivated in multiple myeloma. In vitro functional experiments showed that SOX7 may be acting as a tumor suppressor gene in multiple myeloma by inducing G1 cell cycle arrest and/or apoptosis. Altogether, these results suggest that loss of expression of SOX7 tumor suppressor may be contributing to development of multiple myeloma.
Audience Take Away Notes:
- The audience will gain insight into the role of SOX7 tumor suppressor on multiple myeloma development
- Other faculty may shape their future research on SOX7 and/or multiple myeloma based on the results presented in this talk
- The audience may apply the techniques mentioned in this speech in their
