miR-124-3p is a chronic regulator of gene expression after brain injury.

Cellular and Molecular Life Sciences : CMLS
Niina VuokilaNoora Puhakka

Abstract

Traumatic brain injury (TBI) initiates molecular and cellular pathologies that underlie post-injury morbidities, including hippocampus-related memory decline and epileptogenesis. Non-coding small RNAs are master regulators of gene expression with the potential to affect multiple molecular pathways. To evaluate whether hippocampal gene expression networks are chronically regulated by microRNAs after TBI, we sampled the dentate gyrus of rats with severe TBI induced by lateral fluid-percussion injury 3 months earlier. Ingenuity pathway analysis revealed 30 upregulated miR-124-3p targets, suggesting that miR-124-3p is downregulated post-TBI (z-score = - 5.146, p < 0.05). Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization confirmed the chronic downregulation of miR-124-3p (p < 0.05). Quantitative PCR analysis of two targets, Plp2 and Stat3, indicated that their upregulation correlated with the miR-124-3p downregulation (r = - 0.647, p < 0.05; r = - 0.629, p < 0.05, respectively). Immunohistochemical staining of STAT3 confirmed the increased protein expression. STRING analysis showed that 9 of the 30 miR-124-3p targets belonged to a STAT3 network. Reactome analysis and data mining connected the targets especi...Continue Reading

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Citations

Apr 22, 2020·Cancer Biotherapy & Radiopharmaceuticals·Ximing Gong, Zhenya Zhu
Jul 31, 2020·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Qiu-Xia XiaoYing Zhang
Apr 5, 2020·International Journal of Molecular Sciences·Niina VuokilaAsla Pitkänen
Aug 6, 2020·International Journal of Molecular Sciences·Cora Rebecca SchindlerDirk Henrich
Jun 18, 2020·Nature Reviews. Neurology·Gary P Brennan, David C Henshall
Jul 3, 2021·International Journal of Molecular Sciences·Ana Rita VazDora Brites

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Methods Mentioned

BETA
pharmacotherapies
PCR
dissection
reverse transcription PCR
Assay
RNA Assay
light microscopy
acetylation

Software Mentioned

L1000 Characteristic Direction Signature Search Engine
STRINGv10
GraphPad
Scopus
Gene Set Enrichment Analysis ( GSEA )
L1000CDS2
L1000 Characteristic Direction Signature Search Engine ( L1000CDS
GSEA
L1000CDS
Word Cloud Generator

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