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Long non-coding RNA Peg13 attenuates the sevoflurane toxicity against neural stem cells by sponging microRNA-128-3p to preserve Sox13 expression

Jiang, Yunfeng, Wang, Yue, Sun, Yu, Jiang, Hong·2020·PLOS ONE
DOI 10.1371/journal.pone.0243644PMC PMC7725402
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Abstract

Background: Exposure to anesthetics during brain development may impair neurological function, however, the mechanisms underlying anesthetic neurotoxicity are unclear. Recent studies indicate that long non-coding RNAs (lncRNAs) are crucial for regulating the functional brain development during neurogenesis. This study aimed to determine the regulatory effects and potential mechanisms of lncRNA Peg13 (Peg13) on sevoflurane exposure-related neurotoxicity against neural stem cells (NSCs). Methods: Mouse embryotic NSCs were isolated and their self-renewal and differentiation were characterized by immunofluorescence. NSCs were exposed to 4.1% sevoflurane 2 h daily for three consecutive days. The potential toxicities of sevoflurane against NSCs were evaluated by neurosphere formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and flow cytometry assays. The Peg13, miR-128-3p and Sox13 expression in NSCs were quantified. The potential interactions among Peg13, miR-128-3p and Sox13 were analyzed by luciferase reporter assay. The effects of Peg13 and/or miR-128-3p over-expression on the sevoflurane-related neurotoxicity and Sox13 expression were determined in NSCs. Results: The isolated mouse embryotic NSCs displayed potent self-renewal ability and differentiated into neurons, astrocytes and oligodendrocytes in vitro, which were significantly inhibited by sevoflurane exposure. Sevoflurane exposure significantly down-regulated Peg13 and Sox13, but enhanced miR-128-3p expression in NSCs. Transfection with miR-128-3p mimics, but not the control, significantly mitigated the Peg13 or Sox13-regulated luciferase expression in 293T cells. Peg13 over-expression significantly reduced the sevoflurane-related neurotoxicity and increased Sox13 expression in NSCs, which were mitigated by miR-128-3p transfection. Conclusion: Such data indicated that Peg13 mitigated the sevoflurane-related neurotoxicity by sponging miR-128-3p to preserve Sox13 expression in NSCs.

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Metadata

Authors
Jiang, Y., Wang, Y., Sun, Y., & Jiang, H.
ORCID
Sun, Yu
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2020-12-09
Volume
15
Issue
12
Pages
e0243644
ISSN
1932-6203
DOI
10.1371/journal.pone.0243644
PMC
PMC7725402
Cited by
24
References
2
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Natural Science Foundation of Shanghai (18ZR1422900)

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