ORIGINAL RESEARCH article
Front. Reprod. Health
Sec. Gynecology
Polygala fallax Hemsl. Suppresses Malignant Phenotypes of Ectopic Endometrial Cells via the LINC02381-miR-27a-3p-EGFR Axis and PI3K/Akt Signaling
Provisionally accepted
Chunhong Liao
Ning Li*- Guangxi International Zhuang Medical Hospital, Nanning, China
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[Abstract]Objective: To investigate the effects of Polygala fallax Hemsl. (PFH)-containing serum on proliferation, migration, and invasion of human ectopic endometrial cells (12Z) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, using Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) and network pharmacology. Methods: PFH-containing serum and control serum were prepared from Sprague-Dawley (SD) rats. 12Z cells were treated with control serum or varying concentrations of PFH-containing serum for 24 h. Cell proliferation was assessed using the Incucyte S3 Live-Cell Analysis System to determine the optimal PFH concentration. Based on preclinical data and bioinformatics analysis, we identified mRNA within the ceRNA axis associated with Endometriosis (EMs) pathogenesis and PFH treatment. 12Z cells were transfected with sh-lncRNA or sh-mRNA to knock down lncRNA and mRNA. The proliferation, migration, and invasion of 12Z cells were evaluated after interventions including PI3K/Akt inhibitor (LY294002), PFH-containing serum, combined treatments, lncRNA/mRNA knockdown, and their combinations. Expression levels of lncRNA, mRNA, PI3K, Akt1 mRNA, and proteins (PI3K, p-PI3K, Akt1, p-Akt1) were measured by RT-qPCR and Western blot. Results: Compared to the control serum group, LY294002, PFH-containing serum, and their combination significantly reduced 12Z cell proliferation, migration, and invasion (P<0.05). Q-Orbitrap LC-MS, network pharmacology, and literature analysis identified EGFR as the mRNA and LINC02381 as the lncRNA within the EMs-related ceRNA axis. EGFR knockdown increased LINC02381 mRNA expression in 12Z cells. PFH-containing serum decreased LINC02381 and EGFR mRNA/protein expression (P<0.05) and inhibited PI3K/Akt pathway activation (P<0.05). LINC02381 or EGFR knockdown further enhanced PFH-containing serum ' s inhibitory effects on cell proliferation, migration, invasion, and PI3K/Akt activation (P<0.05). Conclusion: PFH-containing serum inhibits human ectopic endometrial cell proliferation, migration, and invasion by negatively regulating LINC02381 and EGFR expression, thereby antagonizing PI3K/Akt pathway activation, which may contribute to EMs treatment.
Keywords: Polygala fallax Hemsl., Endometriosis, LINC02381-miR-27a-3p-EGFR axis, PI3K/Akt signaling pathway, proliferation, Migration, invasion
Received: 28 Aug 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Liao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ning Li, ningli1978111@163.com
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