期刊
FEBS JOURNAL
卷 285, 期 20, 页码 3835-3848出版社
WILEY
DOI: 10.1111/febs.14635
关键词
ceramide; exosome; HCC; NSMase 1; sphingomyelin
资金
- National Natural Science Foundation of China [81572738]
- Natural Science Foundation of Guangxi [2015GXNSFEA139003]
- Lijiang Scholar Award in Guilin
- High Level of Innovation Team and Outstanding Scholars Program in Colleges and Universities in Guangxi, Hundred Talents Program the Introduction of Overseas High-Level Talents in Colleges and Universities in Guangxi'
Neutral sphingomyelinase 1 (NSMase1) mediates caspase-3 activation and apoptosis. However, the role of NSMase1, especially exosome-borne NSMase1 in hepatocellular carcinoma (HCC), remains unclear. We report that NSMase1, which converts sphingomyelin (SM) to ceramide, was significantly downregulated in HCC tissues. Low NSMase1 expression predicted poor long-term survival of HCC patients. NSMase1 downregulation in HCC resulted in increased SM and reduced ceramide (Cer) that led to an increased SM/Cer ratio. Interestingly, NSMase1 and NSMase activity were also decreased in exosomes isolated from HCC tissues and cell lines. Furthermore, NSMase activity increased in exosomes isolated from the culture medium of L02 cells transfected with pEGFP-C3-NSMase1 (NSMase1-Exo). NSMase1-Exo suppressed HCC cell growth and induced apoptosis via reduction of the SM/Cer ratio. Thus, NSMase1 in exosomes inhibits HCC growth by decreasing the SM/Cer ratio.
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