Regulation of endometriosis by long non-coding RNA SRA through estrogen receptor: research progress

Endometriosis (EMS) is an estrogen-dependent chronic gynecologic condition that affects approximately 10%-15% of women of childbearing age. Long non-coding RNA SRA (lncRNA SRA) was the first identified non-coding RNA that possesses dual functions: it acts as an RNA scaffold and also encodes the SRAP protein. It participates in estrogen signaling by co-activating estrogen receptors. Recent studies have revealed a distinct expression pattern in ectopic lesions of EMS: lncRNA SRA and ERα are coordinately downregulated, whereas SRAP and ERβ are coordinately upregulated. This inverse correlation highlights a unique dual-function switching mechanism of the SRA/SRAP axis in the pathogenesis of EMS. In this review, we systematically summarize the conserved domain features of lncRNA SRA and its dual roles as an RNA scaffold and a protein-coding transcript. We then dissect the molecular mechanisms by which SRA/SRAP influences the ERα/ERβ balance, thereby modulating cell proliferation, apoptosis, and the inflammatory microenvironment in EMS. Based on current evidence, we propose a dual-function switching model: the EMS microenvironment drives alternative splicing of the SRA gene, shifting the output from lncRNA SRA toward SRAP protein. These two products selectively couple with ERα and ERβ, respectively, and jointly reshape estrogen receptor signaling in ectopic endometrial cells. Furthermore, we discuss the clinical translational potential of the lncRNA SRA/SRAP ratio as both a diagnostic biomarker and a therapeutic target, aiming to provide new insight for precision diagnosis and treatment of EMS.