Involvement of circ_0029407 in Caerulein-Evoked Cytotoxicity in Human Pancreatic Cells via the miR-579-3p/TLR4/NF-κB...

Acute pancreatitis (AP) is the most prevalent gastrointestinal inflammatory disease. Circular RNAs (circRNAs) are implicated in the development of AP. Here, we identified the precise action of circ_0029407 in AP development. Human pancreatic epithelial cells (HPECs) were stimulated with caerulein. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays, respectively. Circ_0029407, microRNA (miR)-579-3p, and toll-like receptor 4 (TLR4) were quantified by a qRT-PCR or western blot assay. Dual-luciferase reporter and RNA pull-down assays were performed to evaluate the direct relationship between miR-579-3p and circ_0029407 or TLR4. Our results indicated that circ_0029407 was markedly overexpressed in AP serum samples and caerulein-stimulated HPECs. Reduction of circ_0029407 attenuated caerulein-imposed HPEC damage by promoting cell proliferation and repressing cell apoptosis and inflammation. Mechanistically, circ_0029407 contained a miR-579-3p binding site, and miR-579-3p downregulation reversed the effect of circ_0029407 reduction on caerulein-imposed HPEC damage. TLR4 was identified as a direct and functional target of miR-579-3p, and TLR4 overexpression reversed the impact of miR-579-3p upregulation on attenuating caerulein-imposed HPEC damage. Moreover, circ_0029407 regulated the TLR4/nuclear factor NF-kappaB (NF-κB) signaling by acting as a competing endogenous RNA (ceRNA) for miR-579-3p. Our study suggests that circ_0029407 regulates caerulein-imposed cell injury in human pancreatic cells at least in part via the TLR4/NF-κB signaling pathway by functioning as a ceRNA for miR-579-3p.