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

Cancer Cell International

Hongmei Yang¹  Ning Xu¹  Jiaxin Ye¹  Hairong Xiong¹  Wenjun Hu²  Kairu Xie³  Jian Shi⁴  Zhixian Chen⁴  Daojia Miao⁴  Changfei Yuan⁴  Zhiyong Xiong⁴  Wen Xiao⁴  Xiaoping Zhang⁴ 

[1] Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, China;Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, China;Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, China;Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, China;Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China;Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;

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

DOI  :  10.1186/s12935-021-02332-w

来源: Springer

【 摘 要 】

BackgroundCancer 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.MethodsData 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.ResultsAnalysis 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.ConclusionsThe 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】

CC BY