Exosomal miRNA 16-5p/29a-3p from pancreatic cancer induce adipose atrophy by inhibiting adipogenesis and promoting lipolysis.

ABSTRACT: Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia. MicroRNA sequencing of exosomal components from normal and cancer-derived exosomes revealed enrichment of miR-16-5p, miR-21-5p, miR-29a-3p, and miR-125b-5p in serum exosomes of mice harboring PDAC and patients with PDAC. Further, miR-16-5p and miR-29a-3p inhibited adipogenesis through decreasing Erlin2 and Cmpk1 expression which downregulates C/EBPβ and PPARγ. Synergistically, miR-29a-3p promotes lipolysis through increasing ATGL expression by suppressing MCT1 expression. Furthermore, PDAC-exosomes

SUBMITTER: Tien SC 

PROVIDER: S-EPMC11269291 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature