@article {Liu1301, author = {Ying Liu and Meng Wang and Ting Deng and Rui Liu and Tao Ning and Ming Bai and Guoguang Ying and Haiyang Zhang and Yi Ba}, title = {Exosomal miR-155 from gastric cancer induces cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiation via C/EPBβ}, volume = {19}, number = {9}, pages = {1301--1314}, year = {2022}, doi = {10.20892/j.issn.2095-3941.2021.0220}, publisher = {Cancer Biology \& Medicine}, abstract = {Objective: The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia (CAC) by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer (GC)-associated adipocytes.Methods: Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ, C/EPBα, PPARγ, and UCP1 in adipose mesenchymal stem cells (A-MSCs) to evaluate the function of exosomal miR-155. BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results: Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets. Similarly, A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression (P \< 0.05). Mechanistically, exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ, accompanied by downregulated C/EPBα and PPARγ and upregulated UCP1 (P \< 0.05). Moreover, overexpression of miR-155 in GC exosomes improved CAC in vivo, which was characterized by fat loss, suppressed expressions of C/EPBβ, C/EPBα, and PPARγ in A-MSCs, and high expression of UCP1 (P \< 0.05). Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions: GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβ of A-MSCs, which played a crucial role in CAC.}, issn = {2095-3941}, URL = {https://www.cancerbiomed.org/content/19/9/1301}, eprint = {https://www.cancerbiomed.org/content/19/9/1301.full.pdf}, journal = {Cancer Biology \& Medicine} }