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KCNQ1OT1 mediates keratinocyte migration to promote skin wound healing through the miR-200b-3p/SERP1 axis
Institution:1. Department of Plastic Surgery, Taizhou Central Hospital/Taizhou University Hospital, Taizhou, Zhejiang, China;2. Department of Cardiothoracic Surgery, Taizhou Central Hospital/Taizhou University Hospital, Taizhou, Zhejiang, China;3. Department of Cardiovascular Medicine, Taizhou First People''s Hospital, Taizhou, Zhejiang, China;4. Department of Dermatology, Taizhou First People''s Hospital, Taizhou, Zhejiang, China;1. Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China;2. Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China;3. The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China;4. Huai'' an First People''s Hospital, Nanjing Medical University, Huai an, Jiangsu, China;1. Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, China PRC;2. Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, China PRC;3. Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, China PRC;4. Department of Oral Pathology School of Stomatology, Nanjing Medical University, Nanjing, China PRC;1. Moscow Institute of Physics and Technology (National Research University), Institutsky per. 9, Dolgoprudny, Moscow Region 141701, Russia;2. Research Center of Toxicology and Hygienic Regulation of Biopreparations, NRC Institute of Immunology FMBA of Russia, Ul. Lenina 102A, Dashkovka, Serpukhov district, Moscow Region 142253, Russia;1. Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany;2. Department of Otorhinolaryngology, Head and Neck Surgery, Armed Forces Hospital Ulm, Ulm, Germany;3. Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany;4. Department of Plastic, Hand and Reconstructive Microsurgery, Hand Trauma and Replantation Center, BG Unfallklinik Frankfurt am Main, Germany
Abstract:BackgroundThe basic functions of keratinocyte are crucial steps during skin wound healing. KCNQ1OT1 long noncoding RNA was found to accelerate the migration and proliferation of keratinocyte in psoriasis. Here, we elucidated the action and mechanism of KCNQ1OT1 in skin wound healing.MethodsExpression levels of genes and proteins were evaluated by quantitative real-time PCR (qRT-PCR) and western blotting. Cell migration was assessed by using scratch and transwell assays. The interaction between miR-200b-3p and KCNQ1OT1 or SERP1 (Stress Associated Endoplasmic Reticulum Protein 1) was confirmed by bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and pull-down assay.ResultsKCNQ1OT1 had increased significantly in wound edge 1 day and 7 day after injury. Functionally, overexpression of KCNQ1OT1 promoted keratinocyte migration. Mechanistically, KCNQ1OT1/miR-200b-3p/SERP1 constituted a competing endogenous RNA (ceRNA) network in keratinocytes. A series of rescue experiments showed that miR-200b-3p up-regulation in keratinocytes attenuated the pro-migration action of KCNQ1OT1 in cells. Moreover, knockdown of miR-200b-3p could promote keratinocyte migration, which was abolished by SERP1 silencing. KCNQ1OT1 competitively sponged for miR-200b-3p to elevate the expression of its target SERP1.ConclusionKCNQ1OT1 could promote keratinocyte migration by miR-200b-3p/SERP1 axis, suggesting that KCNQ1OT1 might play a crucial role in skin wound healing.
Keywords:KCNQ1OT1  MiR-200b-3p  SERP1  Keratinocyte  Migration  Wound healing
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