| HRA006698
(Open Access)
|
While accumulating evidence has proved the presence of ERb (estrogen receptor b) expression in TNBC (triple-negative breast cancer), the functional roles ERb in TNBC have been controversial. Our study has demonstrated that the activation of ERb hijacks the splicing machinery to modulate intron retention of 5-oxoprolinase (OPLAH), encoding a critical enzyme OPLAH involved in glutathione metabolism and oxidative stress. Altered splicing of OPLAH results in R-loop formation and DNA damage in TNBC cells. The identification of this molecular mechanism offers broad therapeutic avenues for future development of ERb inhibitor and optimized combination therapies as treatment of TNBCs in the clinical setting. |
