LncRNA MEG3 confers protection against Escherichia coli-triggered endometrial epithelial injury: ceRNA-mediated derepression of the miR‑7/PPARα axis.

Endometritis is a common postpartum reproductive disorder in humans and mammals, often triggered by opportunistic pathogens such as Escherichia coli (E. coli) invading the endometrium. It compromises fertility and imposes substantial economic burdens. Although broad‑spectrum antibiotics remain the mainstay of treatment, their prolonged use has fostered resistance and residue problems, driving the search for safer alternatives. Long non‑coding RNAs are gaining attention as therapeutic candidates, but the involvement of lncRNA MEG3 in endometritis has not been explored. To address this, we established an in vitro inflammatory model by stimulating endometrial epithelial cells with E. coli, and we also collected clinical endometrial tissues from affected animals. Here, we found that MEG3 was markedly downregulated in both inflamed tissues and cells, and predominantly localized in the cytoplasm. This downregulation coincided with Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF‑κB) activation, increased pro-inflammatory cytokines, a pro-apoptotic Bax/Bcl-2 shift with cleaved-Caspase-3, and reactive oxygen species (ROS) accumulation-hallmarks of inflammation, apoptosis, and oxidative stress. Knockdown of MEG3 exacerbated these changes, while overexpression reversed them, pointing to a protective role. Mechanistically, MEG3 directly bound miR‑7 and negatively regulated its expression. miR‑7 overexpression promoted, whereas miR‑7 knockdown alleviated, E. coli‑induced inflammatory injury. Moreover, miR‑7 directly targeted peroxisome proliferator-activated receptor α (PPARα), and PPARα inhibition with MK886 reversed the protective effects of miR‑7 silencing, confirming that miR‑7 acts through PPARα suppression. Importantly, PPARα was found to physically interact with and upregulate Sirtuin 1 (SIRT1); PPARα overexpression suppressed inflammatory responses, apoptosis, and ROS production, effects that were reversed by SIRT1 knockdown. SIRT1 activation via its agonist SRT1720 likewise reduced p‑p65 and acetylated p53 levels, alleviating cellular damage. Taken together, our in vitro data indicate that MEG3 acts as a competing endogenous RNA (ceRNA) that sponges miR‑7, thereby relieving miR‑7‑mediated repression of PPARα. This unleashes the PPARα/SIRT1 axis, which concurrently inhibits p53‑mediated mitochondrial apoptosis and NF‑κB‑driven inflammation by promoting p53 deacetylation and suppressing p65 phosphorylation, ultimately curbing excessive TLR4/NF‑κB signaling, attenuating apoptosis, and reducing oxidative stress. These findings delineate a protective MEG3/miR‑7/PPARα/SIRT1 regulatory axis in endometrial epithelial cells in vitro, providing new mechanistic insights and potential targets for further in vivo validation and precision therapy.