Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition
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Namgyu Lee1, Jung-Hee Kwon2, Young Bae Kim4, Seong-Hoon Kim1, Sung Jin Park1, Weiguang Xu3, Hoe-Yune Jung5, Kyong-Tai Kim1,5, Hee Jung Wang3, Kwan Yong Choi1,5
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea
2Cbs Bioscience Inc., Daejeon, Korea
3Department of Surgery, Ajou University School of Medicine, Suwon, Korea
4Department of Pathology, Ajou University School of Medicine, Suwon, Korea
5Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea
Kwan Yong Choi, e-mail: email@example.com
Keywords: HCC, VRK1, proliferation, cell cycle, luteolin
Received: January 17, 2015 Accepted: August 24, 2015 Published: September 07, 2015
We identified the specific role of vaccinia-related kinase 1 (VRK1) in the progression of hepatocellular carcinoma (HCC) and evaluated its therapeutic and prognostic potential. VRK1 levels were significantly higher in HCC cell lines than a normal hepatic cell line, and were higher in HCC than non-tumor tissue. VRK1 knockdown inhibited the proliferation of SK-Hep1, SH-J1 and Hep3B cells; moreover, depletion of VRK1 suppressed HCC tumor growth in vivo. We also showed that VRK1 knockdown increased the number of G1 arrested cells by decreasing cyclin D1 and p-Rb while upregulating p21 and p27, and that VRK1 depletion downregulated phosphorylation of CREB, a transcription factor regulating CCND1. Additionally, we found that luteolin, a VRK1 inhibitor, suppressed HCC growth in vitro and in vivo, and that the aberrant VRK1 expression correlated with poor prognostic features of HCC. High levels of VRK1 were associated with shorter overall and disease-free survival and higher recurrence rates. Taken together, our findings suggest VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC.
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