Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide
Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide
复制标题
外泌体中性鞘磷脂酶1通过降低鞘磷脂/神经酰胺的比例抑制肝细胞癌
DOI：
10.1111/febs.14635
复制
发表时间：
2018-10-01
期刊：
影响因子：
5.4
通讯作者：
Jin, Junfei
中科院分区：
文献类型：
--
作者：
Lin, Minglin;Liao, Weijia;Jin, Junfei
中性鞘磷脂酶1（NSMase 1）介导caspase-3激活和凋亡。然而，NSMase 1，特别是外泌体携带的NSMase 1在肝细胞癌（HCC）中的作用仍不清楚。我们报道了NSMase 1在肝癌组织中的表达显著下调，NSMase 1可将鞘磷脂（SM）转化为神经酰胺。NSMase 1低表达预示肝癌患者长期生存率低。NSMase 1在HCC中下调导致SM增加和神经酰胺（Cer）减少，从而导致SM/Cer比率增加。有趣的是，NSMase 1和NSMase活性在从HCC组织和细胞系分离的外来体中也降低。此外，在从用pEGFP-C3-NSMase 1转染的L02细胞的培养基中分离的外泌体（NSMase 1-Exo）中，NSMase活性增加。NSMase 1-Exo通过降低SM/Cer比值抑制HCC细胞生长并诱导细胞凋亡。因此，外泌体中的NSMase 1通过降低SM/Cer比率来抑制HCC生长。
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.