4-Nonylphenol regulates cell proliferation and apoptosis in cervical carcinoma through the MEG3/PI3K/AKT signaling pathway

Long non-coding RNAs (lncRNAs) are critical regulators of carcinogenesis; however, their interaction with environmental endocrine disruptors (EEDs) in cervical cancer remains underexplored. This study aimed to investigate the role of lncRNA MEG3 in cervical carcinogenesis and its interaction with 4-Nonylphenol (4-NP), a widespread environmental contaminant. We quantified MEG3 expression using RT-qPCR in clinical specimens and cell lines, and measured urinary 4-NP levels via HPLC-MS/MS. Results showed significant MEG3 downregulation in cervical cancer tissues and elevated 4-NP levels in patients relative to healthy controls (22.37 ± 16.32 vs. 3.84 ± 2.52 ng/mL, P < 0.05). In vitro experiments indicated that 4-NP promoted HeLa cell proliferation (P < 0.05 at 72 h) while suppressing MEG3 expression in dose- and time-dependent manners. Functional restoration of MEG3 via lentiviral overexpression significantly inhibited tumor cell proliferation, migration, invasion, and induced apoptosis (P < 0.05). In vivo xenograft experiments confirmed that MEG3 overexpression suppressed tumor growth (0.03 ± 0.01 g vs. 0.56 ± 0.20 g in controls) by modulating the PI3K-Akt signaling pathway, as indicated by reduced expression of p-AKT, mTOR, PI3K, and BCL-2. Mechanistically, MEG3 overexpression counteracted the oncogenic effects of 4-NP, suggesting MEG3 as a critical mediator of 4-NP-induced carcinogenesis. These findings suggest that MEG3 may counteract 4-NP-induced oncogenic effects, highlighting its potential role as a putative mediator and candidate therapeutic target in environmental chemical-associated cervical carcinogenesis.