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Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia

Forensic diagnosis of fatal hypothermia is considered difficult because there are no specific findings. Accordingly, exploration of novel fatal hypothermia-specific findings is important. To elucidate the molecular mechanism of homeostasis in hypothermia and identify novel molecular markers to infor...

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Autores principales: Umehara, Takahiro, Kagawa, Shinichiro, Tomida, Aiko, Murase, Takehiko, Abe, Yuki, Shingu, Keita, Ikematsu, Kazuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508983/
https://www.ncbi.nlm.nih.gov/pubmed/32963265
http://dx.doi.org/10.1038/s41598-020-71931-w
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author Umehara, Takahiro
Kagawa, Shinichiro
Tomida, Aiko
Murase, Takehiko
Abe, Yuki
Shingu, Keita
Ikematsu, Kazuya
author_facet Umehara, Takahiro
Kagawa, Shinichiro
Tomida, Aiko
Murase, Takehiko
Abe, Yuki
Shingu, Keita
Ikematsu, Kazuya
author_sort Umehara, Takahiro
collection PubMed
description Forensic diagnosis of fatal hypothermia is considered difficult because there are no specific findings. Accordingly, exploration of novel fatal hypothermia-specific findings is important. To elucidate the molecular mechanism of homeostasis in hypothermia and identify novel molecular markers to inform the diagnosis of fatal hypothermia, we focused on microRNA expression in skeletal muscle, which plays a role in cold-induced thermogenesis in mammals. We generated rat models of mild, moderate, and severe hypothermia, and performed body temperature-dependent microRNA expression analysis of the iliopsoas muscle using microarray and quantitative real-time PCR (qRT-PCR). The results show that rno-miR-374-5p expression was significantly induced only by severe hypothermia. Luciferase reporter assay and qRT-PCR results indicated that Mex3B expression was regulated by rno-miR-374-5p and decreased with decreasing body temperature. Gene ontology analysis indicated the involvement of Mex3B in positive regulation of GTPase activity. siRNA analysis showed that Mex3B directly or indirectly regulated Kras expression in vitro, and significantly changed the expression of apoptosis-related genes and proteins. Collectively, these results indicate that rno-miR-374-5p was activated by a decrease in body temperature, whereby it contributed to cell survival by suppressing Mex3B and activating or inactivating Kras. Thus, rno-miR-374-5p is a potential supporting marker for the diagnosis of fatal hypothermia.
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spelling pubmed-75089832020-09-24 Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia Umehara, Takahiro Kagawa, Shinichiro Tomida, Aiko Murase, Takehiko Abe, Yuki Shingu, Keita Ikematsu, Kazuya Sci Rep Article Forensic diagnosis of fatal hypothermia is considered difficult because there are no specific findings. Accordingly, exploration of novel fatal hypothermia-specific findings is important. To elucidate the molecular mechanism of homeostasis in hypothermia and identify novel molecular markers to inform the diagnosis of fatal hypothermia, we focused on microRNA expression in skeletal muscle, which plays a role in cold-induced thermogenesis in mammals. We generated rat models of mild, moderate, and severe hypothermia, and performed body temperature-dependent microRNA expression analysis of the iliopsoas muscle using microarray and quantitative real-time PCR (qRT-PCR). The results show that rno-miR-374-5p expression was significantly induced only by severe hypothermia. Luciferase reporter assay and qRT-PCR results indicated that Mex3B expression was regulated by rno-miR-374-5p and decreased with decreasing body temperature. Gene ontology analysis indicated the involvement of Mex3B in positive regulation of GTPase activity. siRNA analysis showed that Mex3B directly or indirectly regulated Kras expression in vitro, and significantly changed the expression of apoptosis-related genes and proteins. Collectively, these results indicate that rno-miR-374-5p was activated by a decrease in body temperature, whereby it contributed to cell survival by suppressing Mex3B and activating or inactivating Kras. Thus, rno-miR-374-5p is a potential supporting marker for the diagnosis of fatal hypothermia. Nature Publishing Group UK 2020-09-22 /pmc/articles/PMC7508983/ /pubmed/32963265 http://dx.doi.org/10.1038/s41598-020-71931-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Umehara, Takahiro
Kagawa, Shinichiro
Tomida, Aiko
Murase, Takehiko
Abe, Yuki
Shingu, Keita
Ikematsu, Kazuya
Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title_full Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title_fullStr Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title_full_unstemmed Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title_short Body temperature-dependent microRNA expression analysis in rats: rno-miR-374-5p regulates apoptosis in skeletal muscle cells via Mex3B under hypothermia
title_sort body temperature-dependent microrna expression analysis in rats: rno-mir-374-5p regulates apoptosis in skeletal muscle cells via mex3b under hypothermia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508983/
https://www.ncbi.nlm.nih.gov/pubmed/32963265
http://dx.doi.org/10.1038/s41598-020-71931-w
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