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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.
AuthorsDai Shimizu, Mitsuro Kanda, Hiroyuki Sugimoto, Masahiro Shibata, Haruyoshi Tanaka, Hideki Takami, Naoki Iwata, Masamichi Hayashi, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Tsutomu Fujii, Yasuhiro Kodera
JournalInternational journal of oncology (Int J Oncol) Vol. 50 Issue 2 Pg. 381-386 (Feb 2017) ISSN: 1791-2423 [Electronic] Greece
PMID28101581 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (analysis)
  • Blotting, Western
  • Carcinoma, Hepatocellular (enzymology, mortality, pathology)
  • Cell Line, Tumor
  • Female
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Hepatectomy
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms (enzymology, mortality, pathology)
  • Male
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Prognosis
  • Protein-Arginine N-Methyltransferases (metabolism)
  • Treatment Outcome

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