LncRNA NEAT1 Promotes TLR4 Expression to Regulate Lipopolysaccharide-Induced Trophoblastic Cell Pyroptosis as a Molecular Sponge of miR-302b-3p.

Pyroptosis is an inflammation-triggered cell death caused by certain inflammasomes, and long non-coding RNAs (lncRNAs) are related to cell pyroptosis. This study evaluated the mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) on lipopolysaccharide (LPS)-induced trophoblastic cells pyroptosis. HTR-8/Svneo trophoblastic cells were treated with LPS. The expression of lncRNA NEAT1 was decreased using siRNAs, followed by the evaluation of cell proliferation, Caspase-1 activity, levels of Cleaved Caspase-1 and gasdermin D-N, and the concentrations of Interleukin (IL)-1ß and IL-18. We found that LPS promoted the pyroptosis of HTR-8/Svneo cells, and lncRNA NEAT1 was highly expressed in LPS-treated HTR-8/Svneo cells while silencing lncRNA NEAT1 inhibited LPS-induced trophoblastic cells pyroptosis. The subcellular localization of lncRNA NEAT1 was detected. Dual-luciferase gene experiment and RNA pull-down assay detected that lncRNA NEAT1 bound to miR-302b-3p and could inhibit miR-302b-3p, and toll-like receptor 4 (TLR4) was the target gene of miR-302b-3p. Then, a joint experiment was designed for detection, which found that miR-302b-3p downregulation partially reversed the inhibition of silencing lncRNA NEAT1 on LPS-induced trophoblastic cells pyroptosis and overexpression of TLR4 annulled the inhibition of silencing lncRNA NEAT1 on LPS-induced trophoblastic cells pyroptosis. Therefore, lncRNA NEAT1 promoted the transcription of TLR4 by competitively binding to miR-302b-3p, thus promoting LPS-induced trophoblastic cells pyroptosis.