Downregulation Of MiR-29c Induces Muscle Wasting Through Leukemia Inhibitory Factor In Lung Cancer Cachexia

Cancer cachexia is a wasting disorder characterized by significant weight loss,which is attributed to skeletal muscle weakness.In the process of cancer development,micro RNAs act as oncogenes or tumor suppressors.Moreover,they are involved in muscle metabolism and muscle wasting in cachexia.Purpose: This study aims to establish the mechanisms and correlation between mi R-29 c and LIF in muscle wasting in lung cancer cachexia.Methods: Using data from The Cancer Genome Atlas(TCGA)database and q RT-PCR,we evaluated the expression levels of mi R-29 c and Leukemia Inhibitory Factor(LIF).Then,in order to clarify the functions of mi R-29 c and LIF in lung cancer cachexia,we used Lewis lung carcinoma(LLC)cell line to establish the cachexia model and performed in vitro(in C2C12 myotubes)and in vivo(in LLC tumor-bearing mice)experiments.Results: In the lung cancer cachexia model,miR-29 c was found to be down-regulated,and its expression was negatively correlated with muscle catabolic activity.Overexpression of mi R-29 c alleviated the cachectic phenotype.Mechanistically,LIF was shown to be a direct target gene of mi R-29 c,and LIF was upregulated in vitro and in vivo.Furthermore,LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways.Conclusions: mi R-29 c is negatively associated with the cachectic phenotype,and the mi R-29c-LIF axis is a potential therapeutic target for cancer cachexia.