Ying Liu1, Meng Wang1, Ting Deng1, Rui Liu1, Tao Ning1, Ming Bai1, Guoguang Ying1, Haiyang Zhang1, Yi Ba1. 1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
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.
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.
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