title: Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition.
abstract: 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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Namgyu
authors.initials: N
authors.lastname: Lee
authors.affiliation: Cbs Bioscience Inc., Daejeon, Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Hoe-Yune
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.|Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.|Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Kwan Yong
authors.initials: KY
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human
keywords: HCC; VRK1; cell cycle; luteolin; proliferation