LINC00173 silence and estrone supply suppress ER+ breast cancer by estrogen receptor α degradation and LITAF activation

Persistent activation of estrogen receptor alpha (ERα)‐mediated estrogen signaling plays a pivotal role in driving the progression of estrogen receptor positive (ER+) breast cancer (BC). In the current study, LINC00173, a long non‐coding RNA, was found to bind both ERα and lipopolysaccharide (LPS)‐induced tumor necrosis factor alpha (TNFα) factor (LITAF), then cooperatively to inhibit ERα protein degradation by impeding the nuclear export of ERα. Concurrently, LITAF was found to attenuate TNFα transcription after binding to LINC00173, and this attenuating transcriptional effect was quite significant under lipopolysaccharide stimulation. Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF‐transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression. LINC00173, in coordination with lipopolysaccharide‐induced tumor necrosis factor alpha (TNFα) factor (LITAF), enhances the estrogen receptor alpha (ERα) signaling pathway with estradiol, facilitating ERα nuclear enrichment and preventing degradation. Targeting LINC00173 releases LITAF, promoting TNFα transcription with estrone and inducing apoptosis.