Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, China.
FEBS J. 2018 Oct;285(20):3835-3848. doi: 10.1111/febs.14635. Epub 2018 Aug 25.
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.
中性鞘磷脂酶 1（NSMase1）介导半胱天冬酶-3 的激活和细胞凋亡。然而，NSMase1 的作用，特别是外体携带的 NSMase1 在肝细胞癌（HCC）中的作用尚不清楚。我们报告称，将鞘磷脂（SM）转化为神经酰胺的中性鞘磷脂酶 1（NSMase1）在 HCC 组织中显著下调。NSMase1 表达水平低预示着 HCC 患者的长期生存不良。HCC 中 NSMase1 的下调导致 SM 增加和 Cer 减少，从而导致 SM/Cer 比值增加。有趣的是，从 HCC 组织和细胞系分离的外体中也观察到 NSMase1 和 NSMase 活性降低。此外，在转染 pEGFP-C3-NSMase1（NSMase1-Exo）的 L02 细胞的培养基中分离的外体中，NSMase 活性增加。NSMase1-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，外体中的 NSMase1 通过降低 SM/Cer 比值抑制 HCC 生长。
