title: ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kang
authors.forename: Na Young
authors.initials: NY
authors.lastname: Ji
authors.forename: Chung Il
authors.initials: CI
authors.lastname: Lee
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
authors.forename: Dae Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Jong Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Pil Je
authors.initials: PJ
authors.lastname: Park
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Song
mesh_terms: 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
chemical_list: C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering