Xie Kairu, Xiong Hairong, Xiao Wen, Xiong Zhiyong, Hu Wenjun, Ye Jiaxin, Xu Ning, Shi Jian, Yuan Changfei, Chen Zhixian, Miao Daojia, Zhang Xiaoping, Yang Hongmei
Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
Cancer Cell Int. 2021 Nov 27;21(1):627. doi: 10.1186/s12935-021-02332-w.
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.
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.
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.
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.
癌症恶病质是一种以显著体重减轻为特征的消耗性疾病，归因于骨骼肌无力。在癌症发展过程中，微小RNA充当癌基因或肿瘤抑制因子。此外，它们还与肌肉发育和消耗有关。本研究旨在探讨miR-29c与肺癌恶病质中肌肉消耗之间的机制及相关性。
从癌症基因组图谱（TCGA）数据库检索用于表达分析的数据。进行qRT-PCR分析以探究miR-29c和白血病抑制因子（LIF）的表达水平。使用刘易斯肺癌（LLC）细胞系建立恶病质模型，以探究miR-29c和LIF在肺癌恶病质中的功能。此外，进行体外（在C2C12肌管中）和体内（在荷LLC肿瘤小鼠中）实验，以探究miR-29c和LIF在肺恶病质中的机制。
肺癌恶病质模型分析显示miR-29c表达下调，其表达与肌肉分解代谢活性呈负相关。miR-29c过表达减轻了恶病质表型。机制研究表明LIF是miR-29c的直接靶基因，且LIF在体外和体内均上调。分析表明LIF通过JAK/STAT和丝裂原活化蛋白激酶途径促进肌肉消耗。
研究结果表明miR-29c与恶病质表型呈负相关，且miR-29c-LIF轴是癌症恶病质的潜在治疗靶点。
