Targeting LINC00152 activates cAMP/Ca²⁺/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer.

ABSTRACT: Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER+) breast cancer, constituting around 75% of all cases. However, emergence of resistance is common, necessitating the identification of novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen resistance via blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting LINC00152 reduces the mRNA stability of phosphodiesterase 4D (PDE4D), leading to activation of cAMP/PKA/CREB axis and increased expression of TRPC1 Ca²⁺ channel. This causes cytosolic Ca²⁺ overload and generation of reactive oxygen species (ROS) that is, on one hand, accompanied by downregulation of FT

SUBMITTER: Saatci O 

PROVIDER: S-EPMC10942410 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature