title: RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway.
abstract: Aberrant Notch signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell growth. However, the role of Notch signaling in HCC and its underlying mechanism remain elusive. RBP-J-interacting and tubulin-associated (RITA) mediates the nuclear export of RBP-J to tubulin fibers and downregulates Notch-mediated transcription. In this study, we found that RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Our findings indicate that RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC.
authors.affiliation: The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
authors.forename: Haihe
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of General Surgery of Fifth Clinical Hospital of Harbin Medical University, Daqing 163319, China.
authors.forename: Zhanchun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
authors.forename: Shishun
authors.initials: S
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General Surgery of Fifth Clinical Hospital of Harbin Medical University, Daqing 163319, China. Electronic address: zhangyanjie3@aliyun.com.
authors.forename: Guofu
authors.initials: G
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D051996:Transcription Factor RelA / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000072056:Transcription Factor HES-1; D051996:Transcription Factor RelA; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C530104:CCND1 protein, human; C513273:FBXW7 protein, human; C497570:RBPJ protein, human; C498143:RELA protein, human; C495901:TP53 protein, human; C403666:ZNF331 protein, human; C078493:HES1 protein, human; C495894:CDK2 protein, human
keywords: Apoptosis; Cell cycle arrest; HCC; Notch signaling; RITA