PMID- 34423029 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20210929 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2021 DP - 2021 TI - circGLI3 Inhibits Oxidative Stress by Regulating the miR-339-5p/VEGFA Axis in IPEC-J2 Cells. PG - 1086206 LID - 10.1155/2021/1086206 [doi] LID - 1086206 AB - As a new type of noncoding RNA, circular RNA (circRNA) is stable in cells and not easily degraded. This type of RNA can also competitively bind miRNAs to regulate the expression of their target genes. The role of circRNA in the mechanism of intestinal oxidative stress (OS) in weaned piglets is still unclear. In our research, diquat (DQ) was used to induce OS in small intestinal epithelial cells (IPEC-J2) to construct an OS cell model. Mechanistically, dual luciferase reporter assays, fluorescence in situ hybridization (FISH), and western blotting were performed to confirm that circGLI3 directly sponged miR-339-5p and regulated the expression of VEGFA. Overexpression of circGLI3 promoted IPEC-J2 cell proliferation, increased the proportion of S-phase cells (P < 0.01), and reduced reactive oxygen species (ROS) generation when IPEC-J2 cells were subjected to OS. circGLI3 can increase the activity of glutathione peroxidase (GSH-Px) and the total antioxidant capacity (T-AOC) in IPEC-J2 cells and reduce the malondialdehyde (MDA) content and levels of inflammatory factors. Therefore, overexpression of circGLI3 reduced oxidative damage, whereas miR-339-5p mimic counteracted these effects. We identified a regulatory network composed of circGLI3, miR-339-5p, and VEGFA and verified that circGLI3 regulates VEGFA by directly binding miR-339-5p. The expression of VEGFA affects IPEC-J2 cell proliferation, cell cycle progression, and ROS content and changes the levels of antioxidant enzymes and inflammatory factors. This study reveals the molecular mechanism by which circGLI3 inhibits OS in the intestine of piglets and provides a theoretical basis for further research on the effect of OS on intestinal function. CI - Copyright (c) 2021 Zhi-xin Li et al. FAU - Li, Zhi-Xin AU - Li ZX AUID- ORCID: 0000-0002-0218-1680 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Tai'an City, Shandong Province, 271018, China. FAU - Wang, Li-Xue AU - Wang LX AUID- ORCID: 0000-0001-9704-1527 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Tai'an City, Shandong Province, 271018, China. FAU - Zhang, Yu AU - Zhang Y AUID- ORCID: 0000-0002-4326-6031 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Tai'an City, Shandong Province, 271018, China. FAU - Chen, Wei AU - Chen W AUID- ORCID: 0000-0002-2901-5156 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Tai'an City, Shandong Province, 271018, China. FAU - Zeng, Yong-Qing AU - Zeng YQ AUID- ORCID: 0000-0002-0740-2470 AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, No. 61 Daizong Street, Tai'an City, Shandong Province, 271018, China. LA - eng PT - Journal Article DEP - 20210811 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (Vascular Endothelial Growth Factor A) RN - 4Y8F71G49Q (Malondialdehyde) RN - A9A615U4MP (Diquat) RN - EC 1.11.1.9 (Glutathione Peroxidase) SB - IM MH - Animals MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Diquat/*adverse effects MH - Epithelial Cells/chemistry/cytology/drug effects MH - Gene Expression Regulation/drug effects MH - Glutathione Peroxidase/metabolism MH - Intestine, Small/chemistry/*cytology/drug effects MH - Malondialdehyde/metabolism MH - MicroRNAs/*genetics MH - Models, Biological MH - Oxidative Stress MH - RNA, Circular/*genetics MH - Swine MH - Vascular Endothelial Growth Factor A/*genetics/metabolism PMC - PMC8376464 COIS- The authors declare that they have no competing interests. EDAT- 2021/08/24 06:00 MHDA- 2021/09/30 06:00 PMCR- 2021/08/11 CRDT- 2021/08/23 06:38 PHST- 2021/05/18 00:00 [received] PHST- 2021/07/10 00:00 [revised] PHST- 2021/07/26 00:00 [accepted] PHST- 2021/08/23 06:38 [entrez] PHST- 2021/08/24 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2021/08/11 00:00 [pmc-release] AID - 10.1155/2021/1086206 [doi] PST - epublish SO - Biomed Res Int. 2021 Aug 11;2021:1086206. doi: 10.1155/2021/1086206. eCollection 2021.