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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.529544/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Liu-Lin Xiong Liu-Lin Xiong Liu-Lin Xiong Lu-Lu Xue Lu-Lu Xue Ruo-Lan Du Hao-Li Zhou Ya-Xin Tan Ya-Xin Tan Zheng Ma Yuan Jin Zi-Bin Zhang Yang Xu Qiao Hu Larisa Bobrovskaya Xin-Fu Zhou Jia Liu Ting-Hua Wang Ting-Hua Wang |
| spellingShingle |
Liu-Lin Xiong Liu-Lin Xiong Liu-Lin Xiong Lu-Lu Xue Lu-Lu Xue Ruo-Lan Du Hao-Li Zhou Ya-Xin Tan Ya-Xin Tan Zheng Ma Yuan Jin Zi-Bin Zhang Yang Xu Qiao Hu Larisa Bobrovskaya Xin-Fu Zhou Jia Liu Ting-Hua Wang Ting-Hua Wang Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis Frontiers in Cell and Developmental Biology hypoxic ischemic encephalopathy Vi4 miRNA-185-5p IGFBP3 neuron survival cell apoptosis |
| author_facet |
Liu-Lin Xiong Liu-Lin Xiong Liu-Lin Xiong Lu-Lu Xue Lu-Lu Xue Ruo-Lan Du Hao-Li Zhou Ya-Xin Tan Ya-Xin Tan Zheng Ma Yuan Jin Zi-Bin Zhang Yang Xu Qiao Hu Larisa Bobrovskaya Xin-Fu Zhou Jia Liu Ting-Hua Wang Ting-Hua Wang |
| author_sort |
Liu-Lin Xiong |
| 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_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_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_sort |
vi4-mir-185-5p-igfbp3 network protects the brain from neonatal hypoxic ischemic injury via promoting neuron survival and suppressing the cell apoptosis |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cell and Developmental Biology |
| issn |
2296-634X |
| publishDate |
2020-11-01 |
| 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. |
| topic |
hypoxic ischemic encephalopathy Vi4 miRNA-185-5p IGFBP3 neuron survival cell apoptosis |
| url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.529544/full |
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doaj-e770fecfc1594ea6928e88fbe58c8ae52020-11-25T04:10:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.529544529544Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell ApoptosisLiu-Lin Xiong0Liu-Lin Xiong1Liu-Lin Xiong2Lu-Lu Xue3Lu-Lu Xue4Ruo-Lan Du5Hao-Li Zhou6Ya-Xin Tan7Ya-Xin Tan8Zheng Ma9Yuan Jin10Zi-Bin Zhang11Yang Xu12Qiao Hu13Larisa Bobrovskaya14Xin-Fu Zhou15Jia Liu16Ting-Hua Wang17Ting-Hua Wang18Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaSchool of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South AustraliaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaShijiazhuang Maternity and Child Healthcare Hospital, Shijaizhuang, ChinaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaSchool of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South AustraliaSchool of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South AustraliaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaAnimal Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, ChinaNeonatal 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.https://www.frontiersin.org/articles/10.3389/fcell.2020.529544/fullhypoxic ischemic encephalopathyVi4miRNA-185-5pIGFBP3neuron survivalcell apoptosis |