Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification Of A New Role Of miR-199a-5p As Factor Implied In Neuronal Damage: Decreasing The Expression Of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.

Teresa Muñoz-Galdeano
,
David Reigada
* ORCID logo ,
María Gamarra
,
Altea Soto
,
María Asunción Barreda-Manso
ORCID logo ,
Irene Novillo
,
Manuel Nieto-Díaz
ORCID logo ,
Rodrigo M. Maza
* ORCID logo
Version 1 : Received: 30 November 2022 / Approved: 1 December 2022 / Online: 1 December 2022 (09:46:45 CET)
Version 2 : Received: 10 January 2023 / Approved: 11 January 2023 / Online: 11 January 2023 (11:39:24 CET)

How to cite: Muñoz-Galdeano, T.; Reigada, D.; Gamarra, M.; Soto, A.; Barreda-Manso, M. A.; Novillo, I.; Nieto-Díaz, M.; Maza, R. M. Identification Of A New Role Of miR-199a-5p As Factor Implied In Neuronal Damage: Decreasing The Expression Of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.. Preprints 2022, 2022120020. https://doi.org/10.20944/preprints202212.0020.v1 Muñoz-Galdeano, T.; Reigada, D.; Gamarra, M.; Soto, A.; Barreda-Manso, M. A.; Novillo, I.; Nieto-Díaz, M.; Maza, R. M. Identification Of A New Role Of miR-199a-5p As Factor Implied In Neuronal Damage: Decreasing The Expression Of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.. Preprints 2022, 2022120020. https://doi.org/10.20944/preprints202212.0020.v1

Abstract

Altered expression of microRNAs (miRNAs) after spinal cord injury (SCI) has been described as being responsible for the main secondary responses, such as apoptosis. X-linked inhibitor apoptosis protein (XIAP) is a key apoptotic component involved in the progression of apoptotic programmed cell death. Several regulators have been described to modulate the XIAP's function, including the post-transcriptional regulator's miRNAs. The main aim of the present work is to identify miRNAs with altered expression after SCI which can regulate XIAP expression using bioinformatics and prediction algorithms. Our bioinformatic analyses identified several miRNAs candidates whose up-regulation following SCI could be responsible for the down-regulation of XIAP, including miR-199a-5p. We examined the relationship between miR-199a-5p and XIAP and their negative correlation expression levels after SCI and characterized the spatial distribution of miR-199a-5p in uninjured and rat-contused spinal cords, using a specific fluorescent in situ hybridization (FISH) probe for miR-199a-5p. Finally, in vitro simulation of the increment in miR-199a-5p observed after SCI by transfection of a miR-199a-5p mimic into C6 cells confirmed the decrease in XIAP protein levels.. These findings provide new insights into apoptotic miRNAs-mediated mechanisms after SCI, which will help us develop therapeutic strategies based on miRNAs for treating SCI.

Keywords

spinal cord injury; apoptotic cell death; XIAP; neuroprotection; miRNA-based therapies

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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