Downregulation of lncRNA NEAT1 Relieves Caerulein-Induced Cell Apoptosis and Inflammatory Injury in AR42J Cells Through Sponging miR-365a-3p in Acute Pancreatitis

Abstract

Mounting evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs exert a critical regulatory role in acute pancreatitis. The present study aimed to explore the role of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in acute pancreatitis (AP) that was induced by caerulein in rat pancreatic acinar cells (AR42J). The potential target sites of lncRNA NEAT1 and miR-365a-3p were predicted using starBase and were confirmed using dual-luciferase reporter assay. Reverse transcription-quantitative polymerase chain reaction was performed to assess lncRNA NEAT1 and miR-365a-3p expression levels in AP induced by caerulein. Cell Counting Kit-8 and flow cytometry assays were performed to assess AR42J cell viability. Western blotting was performed to evaluate the expression of apoptosis-related proteins. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were detected by ELISA. The results of the dual-luciferase reporter assay confirmed that miR-365a-3p could bind to NEAT1. LncRNA NEAT1 was upregulated in AR42J cells treated with 10 nmol/l caerulein, and miR-365a-3p was expressed at low levels in an AP model. Overexpression of miR-365a-3p suppressed the apoptosis and inflammatory response of AR42J cells induced by caerulein. Importantly, inhibition of lncRNA NEAT1 decreased apoptosis and inflammation in caerulein-treated AR42J cells, while these effects were reverted upon co-transfection with a miR-365a-3p inhibitor. In conclusion, lncRNA NEAT1 was involved in AP progression by sponging miR-365a-3p and may thus be a novel target for treating patients with AP.

Keywords: Acute pancreatitis; Long non-coding RNA; Nuclear paraspeckle assembly transcript 1; microRNA-365a-3p.