The process of apoptosis begins when the balance between proapoptotic and antiapoptotic stimuli is disturbed, leading to oligomerization of apoptosis effectors and disruption of the outer mitochondrial membrane. BCL-2 family proteins are the major regulators of mitochondrial pathway of apoptosis. In turn, microRNA-125b (miR-125b) is a member of microRNAs, which are short single-stranded noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. miR-125b targets messenger RNAs encoding proapoptotic (BAK1, PUMA, BMF) and antiapoptotic (MCL1) BCL-2 family proteins. This mini-review briefly describes the involvement of BCL-2 family proteins in triggering apoptosis. Then, attention is paid to the differences in the activation of apoptosis with doxorubicin and paclitaxel, and finally the effect of miR-125b on paclitaxel- and doxorubicin-induced apoptosis in breast cancer cells is considered. It appears that miR-125b downregulates proteins that are significantly involved in the activation of apoptosis after paclitaxel-induced prolonged mitotic arrest or subsequent DNA damage if mitotic slippage occurs. It seems that high levels of miR-125b may not favor paclitaxel therapy, but reduction of miR-125b levels may increase paclitaxel-induced apoptosis, possibly also genotoxic-induced apoptosis, although adverse effects may also occur including decrease in doxorubicin-induced apoptosis.
Keywords: BCL-2 family; chemotherapy; doxorubicin; drug resistance; microRNA; taxol.
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