Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous study revealed that serum deprivation upregulated human alkaline ceramidase 2 (haCER2) activity and mRNA in HeLa cells, but the mechanism remains unknown. In the present study, serum deprivation also upregulated haCER2 activity in HepG2 human hepatoma cell line cells due to an increase in haCER2 mRNA, in which mRNA transcription, not mRNA stability, is involved. Furthermore, p38 mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathway is involved in haCER2 mRNA upregulation by serum deprivation, and this mechanism may explain why haCER2 is upregulated in human liver cancer. In conclusion, p38 MAPK, AP-1 or haCER2 may be used as targets in liver cancer therapy.
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PMID:p38 mitogen-activated protein kinase/activator protein-1 involved in serum deprivation-induced human alkaline ceramidase 2 upregulation. 2579 47

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It has a poor prognosis because it is often diagnosed at the advanced stage when treatments are limited. In addition, HCC pathogenesis is not fully understood, and this has affected early diagnosis and treatment of this disease. Human alkaline ceramidase 2 (ACER2), a key enzyme that regulates hydrolysis of cellular ceramides, affects cancer cell survival, however its role in HCC has not been well characterized. Our results showed that ACER2 is overexpressed in HCC tissues and cell lines. In addition, high ACER2 protein expression was associated with tumor growth; ACER2 knockdown resulted in decreased cell growth and migration. Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) promoted HCC cell growth, invasion, and migration; SMPDL3B knockdown had a significant inhibitory effect on HCC tumor growth in vivo. Moreover, ACER2 positively regulated the protein level of SMPDL3B. Of note, ACER2/SMPDL3B promoted ceramide hydrolysis and S1P production. This axis induced HCC survival and could be blocked by inhibition of S1P formation. In conclusion, ACER2 promoted HCC cell survival and migration, possibly via SMPDL3B. Thus, inhibition of ACER2/SMPDL3B may be a novel therapeutic target for HCC treatment.
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PMID:Human alkaline ceramidase 2 promotes the growth, invasion, and migration of hepatocellular carcinoma cells via sphingomyelin phosphodiesterase acid-like 3B. 3239 85