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

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

doi:10.3892/or.2018.6402

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

Authors:
- 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
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Affiliations: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
Published online on: April 25, 2018 https://doi.org/10.3892/or.2018.6402
Pages: 536-544

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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 α-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 non-tumor regions. Consistent with the significant 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.

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