Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed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.

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.v2 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.v2

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. Our bioinformatic analyses identified several candidate miRNAs that may regulate XIAP, among which miR-199a-5p may be involved in the downregulation of XIAP after SCI. Gene reporter assays and in vitro analyses in the neural C6 cell line confirmed the targeting of miR-199a-5p on the 3-UTR of the rat XIAP and its post-transcriptional regulation of XIAP protein level, but not at mRNA level. Analyses in a rat model of SCI revealed a trend towards increased expression of miR-199a-5p and a decrease in XIAP protein level at 3 days after injury. Finally, using a specific fluorescent in situ hybridization (FISH) probe for miR-199a-5p, we characterized the expression pattern of miR-199a-5p in cells of uninjured and rat-contused spinal cords. These findings provide new insights into apoptotic miRNA-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

Comments (1)

Comment 1
Received: 11 January 2023
Commenter: Teresa Muñoz-Galdeano
Commenter's Conflict of Interests: Author
Comment: The original manuscript changed after the referee´s revision
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