A novel NUTM2A-AS1/miR-769–5p axis regulates LPS-evoked damage in human dental pulp cells via the TLR4/MYD88/NF-κB signaling

Abstract

Background/purposeLong non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) for microRNAs (miRNAs) to be involved in the pathogenesis of multiple human diseases, including pulpitis. Here, we explored the ceRNA activity of NUTM2A-AS1 in regulating lipopolysaccharide (LPS)-evoked cytotoxicity in human dental pulp cells (HDPCs). Materials and methodsNUTM2A-AS1, miR-769–5p and toll-like receptor 4 (TLR4) were quantified by qRT-PCR and Western blot. Cell viability, proliferation, and apoptosis were detected by XTT, EdU, and flow cytometry assays, respectively. The direct relationship between miR-769–5p and NUTM2A-AS1 or TLR4 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. ResultsNUTM2A-AS1 was upregulated in pulpitis tissues and LPS-exposed HDPCs. NUTM2A-AS1 depletion relieved LPS-evoked cell damage in HDPCs. Mechanistically, NUTM2A-AS1 had a binding site for miR-769–5p, and reduced expression of miR-769–5p reversed NUTM2A-AS1 depletion-mediated alleviative effect on LPS-evoked HDPC damage. TLR4 was a direct miR-769–5p target, and miR-769-5p-mediated inhibition of TLR4 relieved LPS-evoked HDPC damage. Furthermore, NUTM2A-AS1 regulated TLR4 expression by acting as a ceRNA for miR-769–5p, and the NUTM2A-AS1/miR-769–5p axis modulated the TLR4/MYD88/NF-κB pathway in LPS-exposed HDPCs. ConclusionOur findings establish that NUTM2A-AS1 regulates LPS-evoked damage in HDPCs at least partially through the miR-769–5p/TLR4/MYD88/NF-κB pathway.