ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma.
Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The aim of this study was to evaluate endothelial cell-specific molecule-1 (ESM-1) as a hepatocellular carcinoma (HCC) marker and to analyze the effect of ESM-1 gene silencing in hepatocellular carcinoma cells. RT-PCR and Western Blot analysis revealed overexpression of ESM-1 in human HCC liver tissue and in serum from patients with HCC. Sandwich ELISA assay was used for quantitative analysis of ESM-1 in serum. Levels of ESM-1 were significantly elevated in the serum of patients with HCC (n = 40) as compared to serum from patients with hepatitis (AH, n = 40; CH, n = 39) or liver cirrhosis (n = 40) or from healthy subjects (n = 40). The accuracy of ESM-1 for HCC was higher than that of α-fetoprotein (AFP) according to ROC curve analysis. Expression of ESM-1 siRNA decreased cell survival through the inhibition of NF-κB pathway and induced cell cycle arrest by PTEN induction resulting in the inhibition of cyclin D1 in SK-Hep1 cells. Furthermore, ESM-1 silencing inhibited cell migration and invasion of SK-Hep1 cells. This study demonstrates that ESM-1 as a potential tumor marker is overexpressed in most tissues and serum in the presence of HCC and is involved with cell survival, cell cycle progression, migration, and invasion of hepatocellular carcinoma cells. Based on our results, we suggest that ESM-1 or a combination of ESM-1 and AFP is useful markers for diagnosis of HCC and ESM-1 may be useful therapeutic target of hepatocellular carcinoma.
Kang
Yun Hee
YH
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Ji
Na Young
NY
Lee
Chung Il
CI
Lee
Hee Gu
HG
Kim
Jae Wha
JW
Yeom
Young Il
YI
Kim
Dae Ghon
DG
Yoon
Seung Kew
SK
Kim
Jong Wan
JW
Park
Pil Je
PJ
Song
Eun Young
EY
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering