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CircSLC8A1 targets miR-181a-5p/HIF1AN pathway to inhibit the growth,migration and extracellular matrix deposition of human keloid fibroblasts
Institution:1. Department of Plastic Surgery, Fujian Maternal and Child Health Hospital, Fuzhou, Fujian 350000, China;2. Department of Pediatric Burn and Plastic Surgery, Fujian Children''s Hospital, Fuzhou, Fujian 350000, China;1. Department of Occupational Therapy, Royal Brisbane and Women’s Hospital, Herston, 4029 QLD, Australia;2. Discipline of Occupational Therapy, School of Health Sciences and Social Work, Griffith University, QLD 4111, Australia;3. Honorary Associate Professor School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, 4072 QLD Australia;1. Department of Professional Psychology, Bahria University, Islamabad, Pakistan;2. Medicare Hospital, Attock City, Pakistan;1. Burns Unit, Concord Repatriation General Hospital, Sydney, Australia;2. Concord Clinical School, University of Sydney, Sydney, Australia;3. ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, Australia;1. United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States;2. United States Military-Baylor University Graduate Program in Nutrition, Fort Sam Houston, TX, United States;3. Brooke Army Medical Center, Fort Sam Houston, TX, United States
Abstract:BackgroundCircular RNAs (circRNAs) are identified as important regulators in human diseases, including keloid. The purpose of this study is to reveal the role and molecular mechanism of circSLC8A1 in keloid formation.MethodsExpression of circSLC8A1, microRNA (miR)-181a-5p, and hypoxia inducible factor 1 alpha inhibitor (HIF1AN) were detected by quantitative real-time PCR. Protein expression of extracellular matrix (ECM) deposition markers and HIF1AN was detected by western blot analysis. Furthermore, the interaction between miR-181a-5p and circSLC8A1 or HIF1AN was confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay.ResultsExpression of circSLC8A1 was downregulated in keloid tissues and HKFs. Overexpression of circSLC8A1 suppressed HKFs proliferation, migration, ECM deposition, and promoted apoptosis. MiR-181a-5p is targeted by circSLC8A1, and its mimic reversed the effect of circSLC8A1 on the biological function of HKFs. HIF1AN was a target of miR-181a-5p, and it was positively regulated by circSLC8A1. Knockdown of HIF1AN also reversed the negatively regulation of circSLC8A1 on the biological functions of HKFs.ConclusionOur data showed that circSLC8A1 regulates the miR-181a-5p/HIF1AN axis to restrain HKFs biological functions, confirming that circSLC8A1 might serve as a novel therapeutic target for keloids.
Keywords:Keloid  Human keloid fibroblasts  CircSLC8A1  MiR-181a-5p  HIF1AN
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