Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia

Abstract Background Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. T...

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Autores principales:	Kairu Xie, Hairong Xiong, Wen Xiao, Zhiyong Xiong, Wenjun Hu, Jiaxin Ye, Ning Xu, Jian Shi, Changfei Yuan, Zhixian Chen, Daojia Miao, Xiaoping Zhang, Hongmei Yang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Cachexia Muscular atrophy miR-29c Leukemia inhibitory factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3d64fb0556d94f79945d3a64f1bb482c
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spelling	oai:doaj.org-article:3d64fb0556d94f79945d3a64f1bb482c2021-11-28T12:36:49ZDownregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia10.1186/s12935-021-02332-w1475-2867https://doaj.org/article/3d64fb0556d94f79945d3a64f1bb482c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02332-whttps://doaj.org/toc/1475-2867Abstract Background Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. This study sought to explore the mechanisms and correlation between miR-29c and muscle wasting in lung cancer cachexia. Methods Data for expression analysis were retrieved from the Cancer Genome Atlas (TCGA) database. qRT-PCR analyses were performed to explore the expression levels of miR-29c and Leukemia Inhibitory Factor (LIF). Lewis lung carcinoma (LLC) cell line was used to establish a cachexia model to explore the functions of miR-29c and LIF in lung cancer cachexia. Furthermore, in vitro (in C2C12 myotubes) and in vivo (in LLC tumor-bearing mice) experiments were performed to explore the mechanisms of miR-29c and LIF in lung cachexia. Results Analysis of the lung cancer cachexia model showed that miR-29c was down-regulated, and its expression was negatively correlated with muscle catabolic activity. Overexpression of miR-29c mitigated the cachectic phenotype. Mechanistic studies showed that LIF was a direct target gene of miR-29c, and LIF was upregulated in vitro and in vivo. Analysis showed that LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways. Conclusions The findings indicated that miR-29c was negatively correlated with the cachectic phenotype, and the miR-29c-LIF axis is a potential therapeutic target for cancer cachexia.Kairu XieHairong XiongWen XiaoZhiyong XiongWenjun HuJiaxin YeNing XuJian ShiChangfei YuanZhixian ChenDaojia MiaoXiaoping ZhangHongmei YangBMCarticleCachexiaMuscular atrophymiR-29cLeukemia inhibitory factorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cachexia Muscular atrophy miR-29c Leukemia inhibitory factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Cachexia Muscular atrophy miR-29c Leukemia inhibitory factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Kairu Xie Hairong Xiong Wen Xiao Zhiyong Xiong Wenjun Hu Jiaxin Ye Ning Xu Jian Shi Changfei Yuan Zhixian Chen Daojia Miao Xiaoping Zhang Hongmei Yang Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
description	Abstract Background Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. This study sought to explore the mechanisms and correlation between miR-29c and muscle wasting in lung cancer cachexia. Methods Data for expression analysis were retrieved from the Cancer Genome Atlas (TCGA) database. qRT-PCR analyses were performed to explore the expression levels of miR-29c and Leukemia Inhibitory Factor (LIF). Lewis lung carcinoma (LLC) cell line was used to establish a cachexia model to explore the functions of miR-29c and LIF in lung cancer cachexia. Furthermore, in vitro (in C2C12 myotubes) and in vivo (in LLC tumor-bearing mice) experiments were performed to explore the mechanisms of miR-29c and LIF in lung cachexia. Results Analysis of the lung cancer cachexia model showed that miR-29c was down-regulated, and its expression was negatively correlated with muscle catabolic activity. Overexpression of miR-29c mitigated the cachectic phenotype. Mechanistic studies showed that LIF was a direct target gene of miR-29c, and LIF was upregulated in vitro and in vivo. Analysis showed that LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways. Conclusions The findings indicated that miR-29c was negatively correlated with the cachectic phenotype, and the miR-29c-LIF axis is a potential therapeutic target for cancer cachexia.
format	article
author	Kairu Xie Hairong Xiong Wen Xiao Zhiyong Xiong Wenjun Hu Jiaxin Ye Ning Xu Jian Shi Changfei Yuan Zhixian Chen Daojia Miao Xiaoping Zhang Hongmei Yang
author_facet	Kairu Xie Hairong Xiong Wen Xiao Zhiyong Xiong Wenjun Hu Jiaxin Ye Ning Xu Jian Shi Changfei Yuan Zhixian Chen Daojia Miao Xiaoping Zhang Hongmei Yang
author_sort	Kairu Xie
title	Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
title_short	Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
title_full	Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
title_fullStr	Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
title_full_unstemmed	Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
title_sort	downregulation of mir-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3d64fb0556d94f79945d3a64f1bb482c
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Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia

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