Tumor-derived exosomal miR-204 enhances white adipose tissue browning to promote cancer associated cachexia

Cachexia is a wasting disorder of adipose tissues that leads to profound weight loss and frailty. One key characteristic of cachexia is elevated resting energy expenditure, which has been linked to increased fat lipolysis and thermogenesis. Extracellular vesicles (EVs) are serving as new messengers to mediate cell-cell communication in vivo. How tumors induce brown fat activity is unknown. Here, we found that breast cancer increased hypoxia inducible factor 1 subunit alpha (HIF1A) protein modification through extracellular-vesicle-encapsulated miR-204 targeting von Hippel-Lindau tumor suppressor (VHL), plays an important role in wasting by driving lipolysis and thermogenic gene expression in adipose tissues. adipose tissue mRNA profiles upon 10 times of EV (MDA-MB-231 EV) injection treatment through tail vein injection of NSG mice and adipose tissue mRNA from tumour bearing mice