RRC ID 63443
著者 Uranbileg B, Ikeda H, Kurano M, Enooku K, Sato M, Saigusa D, Aoki J, Ishizawa T, Hasegawa K, Kokudo N, Yatomi Y.
タイトル Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.
ジャーナル PLoS One
Abstract Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment.
巻・号 11(2)
ページ e0149462
公開日 2016-1-1
DOI 10.1371/journal.pone.0149462
PII PONE-D-15-52161
PMID 26886371
PMC PMC4757388
MeSH Aldehyde-Lyases / antagonists & inhibitors Aldehyde-Lyases / genetics* Aldehyde-Lyases / metabolism Carcinoma, Hepatocellular / blood supply Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Carcinoma, Hepatocellular / surgery Cell Differentiation / genetics* Cell Line, Tumor Cell Movement Cell Proliferation Gene Expression Regulation, Neoplastic Humans Liver Neoplasms / blood supply Liver Neoplasms / genetics* Liver Neoplasms / pathology Liver Neoplasms / surgery Lysophospholipids / metabolism* Metabolome Neoplasm Invasiveness Neoplasm Recurrence, Local / genetics* Neoplasm Recurrence, Local / pathology Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) / genetics* Phosphotransferases (Alcohol Group Acceptor) / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Risk Factors Sphingosine / analogs & derivatives* Sphingosine / metabolism
IF 2.74
リソース情報
ヒト・動物細胞 PLC/PRF/5