Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: roles of cyclic AMP and p38 mitogen-activated protein kinase.
OBJECTIVE
Fatty acid-CoA ligase 4 (FACL4) is an arachidonate-preferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigate the role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process.


METHODS
We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines.


RESULTS
In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver tissues. In addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overexpression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8-bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression.


CONCLUSIONS
FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.
Liang
Yu-Chih
YC
School of Medical Technology, Taipei Medical University, Taipei, Taiwan, China.
Wu
Chih-Hsiung
CH
Chu
Jan-Show
JS
Wang
Chung-Kwe
CK
Hung
Ling-Fang
LF
Wang
Ying-Jan
YJ
Ho
Yuan-Soon
YS
Chang
Jan-Gowth
JG
Lin
Shyr-Yi
SY
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D034741:RNA, Small Interfering; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase