CT26-Derived Exosomal Mir-19b Induce Lipolysis Of White Adopose In Cancer-Associated Cachexia

Cancer-associated cachexia is a multifactorial syndrome characterized by involuntary weight loss(mainly skeletal muscle and adipose tissue).Although the screening,diagnosis and treatment of cancer-related cachexia has made great progress,it is still a serious medical problem.Studies have shown that the breakdown of adipose tissue occurs before skeletal muscle loss,indicating that adipose tissue plays an important role in the development of cancer-associated cachexia.However,the mechanism of fat breakdown caused by cancer-associated cachexia has rarely been reported.Exosome,type of lipid bilayer vesicle with a diameter of 50 nm to 150 nm,was first found in reticulocytes.Initially exosomes were considered to be cellular waste,but it has recently been found to play an important role in the development of diseases.Nowadays,exosomes have attracted wide attention as a new way of intercellular communication,and more and more researches have been performed on its related functions.Exosomes contain a variety of components,including DNA,mRNA,small RNA,and proteins;and miRNAs are considered to be one of the most important biological components.MicroRNAs are a class of single-stranded non-coding small RNAs with a length of approximately 20nt.MiRNAs bind to the 3’-UTR region of the target mRNA,inhibiting its translation or causing its degradation.Many miRNAs are involved in a variety of functions,such as regulation of the immune system,changes in metabolic processes,and functions of the nervous system.It is note that miRNAs play an important role in the tumourigenesis.Recently,miRNAs have also been found to be involved in the regulation of cancer-associated cachexia.Thus,revealing the mechanism of action of these miRNAs is of great significance for the treatment of cancer-associated cachexia.In this study,We discovered that miR-19b enriched in colorectal cell line CT26-derived exosomes.These miR-19b can be delievered into fat cells and promote the breakdown of white fat cells by down-regulating P110α protein.Our study provides a new target for the treatment of cancer-associated cachexia.