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Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis
Neonatal hypoxic ischemic encephalopathy (HIE) due to birth asphyxia is common and causes severe neurological deficits, without any effective therapies currently available. Neuronal death is an important driving factors of neurological disorders after HIE, but the regulatory mechanisms are still unc...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688014/ https://www.ncbi.nlm.nih.gov/pubmed/33262982 http://dx.doi.org/10.3389/fcell.2020.529544 |
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author | Xiong, Liu-Lin Xue, Lu-Lu Du, Ruo-Lan Zhou, Hao-Li Tan, Ya-Xin Ma, Zheng Jin, Yuan Zhang, Zi-Bin Xu, Yang Hu, Qiao Bobrovskaya, Larisa Zhou, Xin-Fu Liu, Jia Wang, Ting-Hua |
author_facet | Xiong, Liu-Lin Xue, Lu-Lu Du, Ruo-Lan Zhou, Hao-Li Tan, Ya-Xin Ma, Zheng Jin, Yuan Zhang, Zi-Bin Xu, Yang Hu, Qiao Bobrovskaya, Larisa Zhou, Xin-Fu Liu, Jia Wang, Ting-Hua |
author_sort | Xiong, Liu-Lin |
collection | PubMed |
description | Neonatal hypoxic ischemic encephalopathy (HIE) due to birth asphyxia is common and causes severe neurological deficits, without any effective therapies currently available. Neuronal death is an important driving factors of neurological disorders after HIE, but the regulatory mechanisms are still uncertain. Long non-coding RNA (lncRNA) or ceRNA network act as a significant regulator in neuroregeneration and neuronal apoptosis, thus owning a great potential as therapeutic targets in HIE. Here, we found a new lncRNA, is the most functional in targeting the Igfbp3 gene in HIE, which enriched in the cell growth and cell apoptosis processes. In addition, luciferase reporter assay showed competitive regulatory binding sites to the target gene Igfbp3 between TCONS00044054 (Vi4) and miR-185-5p. The change in blood miR-185-5p and Igfbp3 expression is further confirmed in patients with brain ischemia. Moreover, Vi4 overexpression and miR-185-5p knock-out promote the neuron survival and neurite growth, and suppress the cell apoptosis, then further improve the motor and cognitive deficits in rats with HIE, while Igfbp3 interfering got the opposite results. Together, Vi4-miR-185-5p-Igfbp3 regulatory network plays an important role in neuron survival and cell apoptosis and further promote the neuro-functional recovery from HIE, therefore is a likely a drug target for HIE therapy. |
format | Online Article Text |
id | pubmed-7688014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76880142020-11-30 Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis Xiong, Liu-Lin Xue, Lu-Lu Du, Ruo-Lan Zhou, Hao-Li Tan, Ya-Xin Ma, Zheng Jin, Yuan Zhang, Zi-Bin Xu, Yang Hu, Qiao Bobrovskaya, Larisa Zhou, Xin-Fu Liu, Jia Wang, Ting-Hua Front Cell Dev Biol Cell and Developmental Biology Neonatal hypoxic ischemic encephalopathy (HIE) due to birth asphyxia is common and causes severe neurological deficits, without any effective therapies currently available. Neuronal death is an important driving factors of neurological disorders after HIE, but the regulatory mechanisms are still uncertain. Long non-coding RNA (lncRNA) or ceRNA network act as a significant regulator in neuroregeneration and neuronal apoptosis, thus owning a great potential as therapeutic targets in HIE. Here, we found a new lncRNA, is the most functional in targeting the Igfbp3 gene in HIE, which enriched in the cell growth and cell apoptosis processes. In addition, luciferase reporter assay showed competitive regulatory binding sites to the target gene Igfbp3 between TCONS00044054 (Vi4) and miR-185-5p. The change in blood miR-185-5p and Igfbp3 expression is further confirmed in patients with brain ischemia. Moreover, Vi4 overexpression and miR-185-5p knock-out promote the neuron survival and neurite growth, and suppress the cell apoptosis, then further improve the motor and cognitive deficits in rats with HIE, while Igfbp3 interfering got the opposite results. Together, Vi4-miR-185-5p-Igfbp3 regulatory network plays an important role in neuron survival and cell apoptosis and further promote the neuro-functional recovery from HIE, therefore is a likely a drug target for HIE therapy. Frontiers Media S.A. 2020-11-09 /pmc/articles/PMC7688014/ /pubmed/33262982 http://dx.doi.org/10.3389/fcell.2020.529544 Text en Copyright © 2020 Xiong, Xue, Du, Zhou, Tan, Ma, Jin, Zhang, Xu, Hu, Bobrovskaya, Zhou, Liu and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Xiong, Liu-Lin Xue, Lu-Lu Du, Ruo-Lan Zhou, Hao-Li Tan, Ya-Xin Ma, Zheng Jin, Yuan Zhang, Zi-Bin Xu, Yang Hu, Qiao Bobrovskaya, Larisa Zhou, Xin-Fu Liu, Jia Wang, Ting-Hua Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title | Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title_full | Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title_fullStr | Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title_full_unstemmed | Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title_short | Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis |
title_sort | vi4-mir-185-5p-igfbp3 network protects the brain from neonatal hypoxic ischemic injury via promoting neuron survival and suppressing the cell apoptosis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688014/ https://www.ncbi.nlm.nih.gov/pubmed/33262982 http://dx.doi.org/10.3389/fcell.2020.529544 |
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