Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 144, Issue 10, Pages 2501-2515Publisher
WILEY
DOI: 10.1002/ijc.31977
Keywords
exosome; circRNA; WAT browning; cachexia; gastric cancer
Categories
Funding
- National Natural Science Foundation of China [81772629, 81602158, 81602156, 81802363, 81702437, 81702275, 81702431, 81772843]
- Tianjin health and family planning commission foundation of science and technology [15KG142]
- Science & Technology Development Fund of Tianjin Education Commission for Higher Education [2018KJ046]
- Nature Science Foundation of Tianjin City [16PTSYJC00170]
- CAMS Innovation Fund for Medical Sciences [2017-I2M-BR-13, 2016-I2M-1-017]
- Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs [2018ZX09206004]
- Individualized Medical Platform of National Clinical Research Center for Cancer [13ZCZCSY20300]
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Cancer-related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are a novel family of endogenous noncoding RNAs that have been proposed to regulate gene expression in mammals. Exosomes are small vesicles derived from cells, and recent studies have shown that circRNAs are stable in exosomes. However, little is known about the biological role of circRNAs in exosomes. In our study, we showed that circRNAs in plasma exosomes have specific expression features in gastric cancer (GC), and ciRS-133 is linked with the browning of white adipose tissue (WAT) in GC patients. Exosomes derived from GC cells deliver ciRS-133 into preadipocytes, promoting the differentiation of preadipocytes into brown-like cells by activating PRDM16 and suppressing miR-133. Moreover, knockdown of ciRS-133 reduced cancer cachexia in tumor-implanted mice, decreasing oxygen consumption and heat production. Thus, exosome-delivered circRNAs are involved in WAT browning and play a key role in cancer-associated cachexia.
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