Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells

Ju Yeon Jeon, Jee San Lee, Eun Ran Park, Yan Nan Shen, Mi Yeun Kim, Hyun Jin Shin, Hyun Yoo Joo, Eung Ho Cho, Sun Mi Moon, Ui Sup Shin, Sun Hoo Park, Chul Ju Han, Dong Wook Choi, Man Bock Gu, Sang Bum Kim, Kee Ho Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher a-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched nontumor regions. Consistent with the signifcant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

Original languageEnglish
Pages (from-to)536-544
Number of pages9
JournalOncology Reports
Volume40
Issue number1
DOIs
Publication statusPublished - 2018 Jul 1

Keywords

  • A-fetoprotein
  • Colon cancer
  • Differentiation
  • Hepatocellular carcinoma
  • Invasion
  • PRMT5

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Jeon, J. Y., Lee, J. S., Park, E. R., Shen, Y. N., Kim, M. Y., Shin, H. J., Joo, H. Y., Cho, E. H., Moon, S. M., Shin, U. S., Park, S. H., Han, C. J., Choi, D. W., Gu, M. B., Kim, S. B., & Lee, K. H. (2018). Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells. Oncology Reports, 40(1), 536-544. https://doi.org/10.3892/or.2018.6402