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KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke

Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in p...

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Autores principales: Yu, Shijia, Yu, Mingjun, He, Xin, Wen, Lulu, Bu, Zhongqi, Feng, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516167/
https://www.ncbi.nlm.nih.gov/pubmed/30945454
http://dx.doi.org/10.1111/acel.12940
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author Yu, Shijia
Yu, Mingjun
He, Xin
Wen, Lulu
Bu, Zhongqi
Feng, Juan
author_facet Yu, Shijia
Yu, Mingjun
He, Xin
Wen, Lulu
Bu, Zhongqi
Feng, Juan
author_sort Yu, Shijia
collection PubMed
description Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. In this study, we revealed that potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) was significantly upregulated in ischemic stroke. Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in transient middle cerebral artery occlusion (tMCAO) mice. Mechanistically, KCNQ1OT1 acted as a competing endogenous RNA of miR‐200a to regulate downstream forkhead box O3 (FOXO3) expression, which is a transcriptional regulator of ATG7. Knockdown of KCNQ1OT1 might inhibit I/R‐induced autophagy and increase cell viability via the miR‐200a/FOXO3/ATG7 pathway. This finding offers a potential novel strategy for ischemic stroke therapy.
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spelling pubmed-65161672019-06-01 KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke Yu, Shijia Yu, Mingjun He, Xin Wen, Lulu Bu, Zhongqi Feng, Juan Aging Cell Original Article Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. In this study, we revealed that potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) was significantly upregulated in ischemic stroke. Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in transient middle cerebral artery occlusion (tMCAO) mice. Mechanistically, KCNQ1OT1 acted as a competing endogenous RNA of miR‐200a to regulate downstream forkhead box O3 (FOXO3) expression, which is a transcriptional regulator of ATG7. Knockdown of KCNQ1OT1 might inhibit I/R‐induced autophagy and increase cell viability via the miR‐200a/FOXO3/ATG7 pathway. This finding offers a potential novel strategy for ischemic stroke therapy. John Wiley and Sons Inc. 2019-04-03 2019-06 /pmc/articles/PMC6516167/ /pubmed/30945454 http://dx.doi.org/10.1111/acel.12940 Text en © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Yu, Shijia
Yu, Mingjun
He, Xin
Wen, Lulu
Bu, Zhongqi
Feng, Juan
KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title_full KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title_fullStr KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title_full_unstemmed KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title_short KCNQ1OT1 promotes autophagy by regulating miR‐200a/FOXO3/ATG7 pathway in cerebral ischemic stroke
title_sort kcnq1ot1 promotes autophagy by regulating mir‐200a/foxo3/atg7 pathway in cerebral ischemic stroke
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516167/
https://www.ncbi.nlm.nih.gov/pubmed/30945454
http://dx.doi.org/10.1111/acel.12940
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