NEAT1-Mediated Intestinal Barrier Dysfunction Through miR-29b-3p Binding in Lipopolysaccharide-Damaged Caco-2 Cells.

The pathogenesis of irritable bowel syndrome with diarrhea (IBS-D) is unclear, and available therapies remain limited. This study evaluated the diagnostic value of NEAT1 in IBS-D and explored its potential regulatory mechanism. A total of 116 patients with IBS-D and 116 healthy controls were included. Serum NEAT1 and miR-29b-3p levels were detected by reverse transcription quantitative real-time PCR (RT-qPCR), and receiver operating characteristic (ROC) curves were used to evaluate diagnostic value. For mechanistic studies, a lipopolysaccharide (LPS)-treated Caco-2 intestinal epithelial cell model was established. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay, apoptosis by flow cytometry, barrier integrity by transepithelial electrical resistance (TEER), and mRNA levels of ZO-1, occludin, and claudin-2 by RT-qPCR. Dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays were used to verify the binding relationship between NEAT1 and miR-29b-3p. NEAT1 was highly expressed, and miR-29b-3p was lowly expressed in patients with IBS-D, and their levels showed a strong negative correlation. NEAT1 knockdown increased miR-29b-3p levels, enhanced cell viability and TEER, reduced apoptosis, increased ZO-1 and occludin mRNA levels, decreased claudin-2 mRNA levels, and alleviated barrier injury-associated readouts in LPS-treated Caco-2 cells. Together, these results indicate that serum NEAT1 is a candidate biomarker for IBS-D and that the NEAT1/miR-29b-3p axis may be involved in intestinal barrier dysfunction.