RRC ID 44719
著者 Uranbileg B, Enooku K, Soroida Y, Ohkawa R, Kudo Y, Nakagawa H, Tateishi R, Yoshida H, Shinzawa S, Moriya K, Ohtomo N, Nishikawa T, Inoue Y, Tomiya T, Kojima S, Matsuura T, Koike K, Yatomi Y, Ikeda H.
タイトル High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.
ジャーナル Int J Cancer
Abstract We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non-tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤ 19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis.
巻・号 134(9)
ページ 2189-98
公開日 2014-5-1
DOI 10.1002/ijc.28547
PMID 24174293
MeSH Animals Carcinoma, Hepatocellular / enzymology* Carcinoma, Hepatocellular / mortality Carcinoma, Hepatocellular / pathology Creatine Kinase, Mitochondrial Form / metabolism* Female Humans Immunoblotting Liver Neoplasms / enzymology* Liver Neoplasms / mortality Liver Neoplasms / pathology Male Mice Mice, Transgenic Middle Aged Prognosis RNA, Small Interfering Real-Time Polymerase Chain Reaction Suppressor of Cytokine Signaling Proteins / metabolism Transfection
IF 5.145
引用数 13
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Hep G2