The following is a summary of “Comprehensive analysis of microRNAs modulated by histone deacetylase inhibitors identifies microRNA-7-5p with anti-myeloma effect,” published in the July 2024 issue of Hematology by Yamada et al.
Due to the challenge of treating multiple myeloma (MM), studies are exploring the potential of Histone deacetylase (HDAC) and MicroRNAs (miRNAs), two epigenetic regulators, for novel therapies.
Researchers conducted a retrospective study to comprehensively identify miRNAs affected by inhibitors of HDAC in myeloma cells.
They found inhibitors of HDAC, as epigenetic regulators, appealing but limited in use. The miRNAs were identified with another epigenetic regulator crucial for future therapeutic advances. The miRNAs were extensively investigated and modified by inhibitors of HDAC in myeloma cells.
The results showed that miR-7-5p (miR-7) was downregulated by HDAC. Myeloma cell lines transfected with miR-7 exhibited reduced proliferation, increased apoptosis, and heightened sensitivity to the inhibitors of HDAC panobinostat. The expression of miR-7 decreased with c-Myc inhibition and increased with bortezomib. Four miR-7 targets were identified as SLC6A9, LRRC59, EXOSC2, and PSME3. PSME3, an oncogene associated with proteasome function in myeloma cells, was the primary focus. PSME3 knockdown led to increased death of myeloma cells and enhanced sensitivity to panobinostat.
Investigators identified miR-7, downregulated by inhibitors of HDAC and targeting PSME3, as a potential therapeutic target due to its role in HDAC resistance and the need for miRNA-based treatment strategies.
Source: link.springer.com/article/10.1007/s12185-024-03812-1
