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

Cancer Cell International

卷:21

Hairong Xiong¹  Wenjun Hu¹  Hongmei Yang¹  Jiaxin Ye¹  Ning Xu¹  Kairu Xie¹  Wen Xiao²  Daojia Miao²  Changfei Yuan²  Zhiyong Xiong²  Zhixian Chen²  Jian Shi²  Xiaoping Zhang² 

[1] Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology;

[2] Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;

关键词: Cachexia;    Muscular atrophy;    miR-29c;    Leukemia inhibitory factor;   

DOI  :  10.1186/s12935-021-02332-w

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown