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

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Abstract

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.

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  1. Xingwen Lu and Caiyan Shi contributed equally to this paper.

Authors and Affiliations

  1. Department of Intensive Care Medicine, Baoan Central Hospital of Shenzhen, Shenzhen, 518102, Guangdong, China

    Xingwen Lu

  2. Department of Medical Oncology and Radiotherapy, Hainan West Central Hospital, Danzhou, 571700, Hainan, China

    Caiyan Shi

  3. Department of Clinical Laboratory, Ganzhou People’s Hospital, No. 18, Meiguan Avenue, Ganzhou, 341000, Jiangxi, China

    Cunlin Fan

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Lu, X., Shi, C. & Fan, C. Involvement of circ_0029407 in Caerulein-Evoked Cytotoxicity in Human Pancreatic Cells via the miR-579-3p/TLR4/NF-κB Pathway. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01175-w

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