PRMT5 and cancer: Interestingly, a recent epigenetic study demonstrated that major histone-modifying enzymes, such as HDAC2, EZH2, and PRMT5, are significantly downregulated in doxorubicin-resistant MCF7 cells [25], suggesting that downregulation or loss of certain regulators in chromatic remodeling may also play an important role in promoting the development of cancer drug resistance.