Chronic myeloid leukemia‐derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR‐92a‐3p. Issue 11 (6th May 2019)

• Record Type: Journal Article
• Authors: Wan, Zhuo; Chen, Xutao; Gao, Xiaotong; Dong, Yan; Zhao, Yingxin; Wei, Mengying; Fan, Wen; Yang, Guodong; Liu, Li
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 11(2019:Nov.)
• Page Start: 21274
• Page End: 21283
• Publication Date: 2019-05-06
• Subjects: adipogenesis -- cachexia -- exosomes -- leukemia; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28732
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Cancer‐associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. Here, we showed that mice injected with CML‐derived exosomes had significant weight loss and great drop of body fat rate. In the meanwhile, we found that CML‐derived exosomes could be taken up by adipose tissue, and, in turn, suppressed the adipogenic ability of adipose‐derived mesenchymal stem cells (ADSCs). By RNA sequencing, miR‐92a‐3p was found highly expressed in both CML cells and the derivative exosomes. Mechanistically, miR‐92a‐3p inhibited adipogenesis of ADSCs via posttranscriptionally decreasing C/EBPα expression when transferred into the ADSCs with the exosomes, and encapsulating miR‐92a‐3p inhibitor into CML exosomes blocked the antiadipogenic effects of CML exosomes. In addition, we also found that miR‐92a‐3p was highly expressed in exosomes from some other types of cancers that cause cachexia. These results demonstrate that adipogenesis inhibition by tumor‐derived exosomes, mainly exosomal microRNAs like miR‐92a‐3p, are the main mediators for CAC. Abstract : Cancer‐associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. In this study, we for the first time revealed that the CML cells could attenuate adipogenesis of adipose‐derived mesenchymal stem cell (ADSC) via secreted exosomes.