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Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide
Author(s) -
Lin Minglin,
Liao Weijia,
Dong Mingjun,
Zhu Rongping,
Xiao Juan,
Sun Tian,
Chen Zhiyong,
Wu Bin,
Jin Junfei
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14635
Subject(s) - ceramide , sphingomyelin , microvesicles , apoptosis , exosome , hepatocellular carcinoma , downregulation and upregulation , cancer research , chemistry , cell growth , cell culture , microbiology and biotechnology , biology , biochemistry , cholesterol , microrna , gene , genetics
Neutral sphingomyelinase 1 ( NSM ase1) mediates caspase‐3 activation and apoptosis. However, the role of NSM ase1, especially exosome‐borne NSM ase1 in hepatocellular carcinoma ( HCC ), remains unclear. We report that NSM ase1, which converts sphingomyelin ( SM ) to ceramide, was significantly downregulated in HCC tissues. Low NSM ase1 expression predicted poor long‐term survival of HCC patients. NSM ase1 downregulation in HCC resulted in increased SM and reduced ceramide (Cer) that led to an increased SM /Cer ratio. Interestingly, NSM ase1 and NSM ase activity were also decreased in exosomes isolated from HCC tissues and cell lines. Furthermore, NSM ase activity increased in exosomes isolated from the culture medium of L02 cells transfected with pEGFP ‐C3‐ NSM ase1 ( NSM ase1‐Exo). NSM ase1‐Exo suppressed HCC cell growth and induced apoptosis via reduction of the SM /Cer ratio. Thus, NSM ase1 in exosomes inhibits HCC growth by decreasing the SM /Cer ratio.