title: RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis.
abstract: RBP-J-interacting and tubulin-associated (RITA) is a novel RBP-J-interacting protein that downregulates Notch-mediated transcription. The current study focuses on the antitumor effect of RITA in human hepatocellular carcinoma (HCC) and aims to explore its molecular mechanism. Thirty paired HCC and adjacent non-tumoral liver samples were analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RITA overexpression was induced by transfection of a pcDNA3.1-Flag-RITA plasmid into HepG2 cells. RITA knockdown was achieved by siRNA transfection. mRNA and protein expression of target genes were quantified by qRT-PCR and Western blotting, respectively. Cell proliferation and apoptosis were measured using MTT assay and flow cytometry. Our results demonstrate that adjacent nontumoral liver samples exhibited increased RITA expression compared to HCC tissues (p < 0.05); RITA levels were associated with tumor differentiation status. Overexpression of RITA suppressed cell proliferation and promoted early apoptosis, while its silencing promoted cell growth dramatically (p < 0.05). RITA overexpression upregulated p53 and reduced cyclin E levels, whereas silencing of RITA had the opposite effect on p53 and cyclin E expression. Our in vitro results represent the first evidence that RITA might suppress tumor growth and induce apoptosis in HCCs, and may be a potent antitumoral agent for HCC treatment that deserves further exploration.
authors.affiliation: Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing, China. wanghaihe4@yahoo.com.cn
authors.forename: Haihe
authors.initials: H
authors.lastname: Wang
authors.forename: Guofu
authors.initials: G
authors.lastname: Chen
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Wang
authors.forename: Chunbo
authors.initials: C
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019927:Cyclin E; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D051880:Receptors, Notch; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C403666:ZNF331 protein, human