Figure 2.

LncRNAs-mediated endocrine therapy resistance. LncRNA TMPO-AS1 directly interacts and stabilizes the mRNA of the ERα encoding gene ESR1, leading to the hyper-proliferation of ER⁺ BC and endocrine resistance. In addition, linc-RoR promotes the degradation of the ERK-specific phosphatase DUSP7 thus enhancing ERK phosphorylation. The upregulation of MAPK/ERK pathway activates ER signaling independent of estrogen, resulting in intrinsic resistance to endocrine therapy. Furthermore, HOTAIR is transcriptionally suppressed by ER. Upon blocking ER signaling through endocrine therapy, HOTAIR is upregulated and promotes the expression of ER at the protein level, leaing to enhanced transcriptional activity of ER and accelerated endocrine resistance.