Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury

Deborah Kennedy Boone, Harris A. Weisz, Min Bi, Michael T. Falduto, Karen E.O. Torres, Hannah E. Willey, Christina M. Volsko, Anjali M. Kumar, Maria Micci, Douglas Dewitt, Donald Prough, Helen Hellmich

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes-we previously found these dysregulated in dying and surviving rat hippocampal neurons-that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes-involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling-whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.

Original languageEnglish (US)
Article number6645
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Essential Genes
MicroRNAs
Cell Death
Genes
Neurons
Neuronal Plasticity
Computational Biology
Energy Metabolism
Regeneration
Cell Survival
Cell Cycle
Maintenance
Traumatic Brain Injury
RNA
Brain

ASJC Scopus subject areas

  • General

Cite this

Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury. / Boone, Deborah Kennedy; Weisz, Harris A.; Bi, Min; Falduto, Michael T.; Torres, Karen E.O.; Willey, Hannah E.; Volsko, Christina M.; Kumar, Anjali M.; Micci, Maria; Dewitt, Douglas; Prough, Donald; Hellmich, Helen.

In: Scientific Reports, Vol. 7, No. 1, 6645, 01.12.2017.

Research output: Contribution to journalArticle

Boone, Deborah Kennedy ; Weisz, Harris A. ; Bi, Min ; Falduto, Michael T. ; Torres, Karen E.O. ; Willey, Hannah E. ; Volsko, Christina M. ; Kumar, Anjali M. ; Micci, Maria ; Dewitt, Douglas ; Prough, Donald ; Hellmich, Helen. / Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{a5249bbedc9447a693059e80b27527dd,
title = "Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury",
abstract = "The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes-we previously found these dysregulated in dying and surviving rat hippocampal neurons-that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes-involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling-whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.",
author = "Boone, {Deborah Kennedy} and Weisz, {Harris A.} and Min Bi and Falduto, {Michael T.} and Torres, {Karen E.O.} and Willey, {Hannah E.} and Volsko, {Christina M.} and Kumar, {Anjali M.} and Maria Micci and Douglas Dewitt and Donald Prough and Helen Hellmich",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-06341-6",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury

AU - Boone, Deborah Kennedy

AU - Weisz, Harris A.

AU - Bi, Min

AU - Falduto, Michael T.

AU - Torres, Karen E.O.

AU - Willey, Hannah E.

AU - Volsko, Christina M.

AU - Kumar, Anjali M.

AU - Micci, Maria

AU - Dewitt, Douglas

AU - Prough, Donald

AU - Hellmich, Helen

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes-we previously found these dysregulated in dying and surviving rat hippocampal neurons-that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes-involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling-whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.

AB - The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes-we previously found these dysregulated in dying and surviving rat hippocampal neurons-that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes-involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling-whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.

UR - http://www.scopus.com/inward/record.url?scp=85026409364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026409364&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-06341-6

DO - 10.1038/s41598-017-06341-6

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 6645

ER -