Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR-146b-5p

Cancer cachexia is a complex syndrome that is associated with thermogenic gene regulation. Currently, although some studies have reported the link between exosomes and cancer cachexia in a few types of cancer, the underlying mechanisms remain poorly understood. In this study, we tried to identify whether exosomes derived from colorectal cancer could affect lipolysis in vitro and in vivo. Here, we collected the tissue samples from 48 patients with colorectal cancer (47.91% females and mean age 55 +/- 8.20) and 48 healthy people at the First Affiliated Hospital of Nanjing Medical University to detect the miR-146-5p expression. Here, we found that cancer cells released exosomes induced white adipose tissues (WATs) browning and accelerated lipolysis. We also demonstrated that miR-146b-5p was enriched in cancer-related exosomes. Overexpression miR-146b-5p resulted in increased WAT browning, decreased oxygen consumption, and fat mass loss (14.57%). The further study identified that miR-146b-5p could directly repress the downstream gene homeodomain-containing gene C10 (HOXC10), thereby regulating lipolysis. Therefore, our results indicated that cancer cells derived from exosomal miR-146b-5p played an essential role in WAT browning. Inhibition of cancer-related exosomes might be necessary for improving the cachexia condition.