title: The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy.
abstract: The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takami
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases