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    標題: Intestine-specific homeobox (ISX) upregulates E2F1 expression and related oncogenic activities in HCC
    作者: Wang, Shen-Nien
    Wang, Li-Ting
    Sun, Ding-Ping
    Chai, Chee-Yin
    Hsi, Edward
    Kuo, Hsing-Tao
    Yokoyama, Kazunari K.
    Hsu, Shih-Hsien
    貢獻者: Kaohsiung Med Univ Hosp, Div Hepatobiliary Surg, Dept Surg, Fac Med
    Kaohsiung Med Univ, Grad Inst Med, Coll Med
    Chi Mei Med Ctr, Div Gen Surg, Dept Surg
    Chia Nan Univ Pharm & Sci, Dept Food Sci & Technol
    Coll Med, Dept Pathol, Fac Med
    Kaohsiung Med Univ, Dept Genome Med, Coll Med
    Chi Mei Med Ctr, Div Hepatogastroenterol, Dept Internal Med
    Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management
    Kaohsiung Med Univ, Res Ctr Stem Cell Res
    Kaohsiung Med Univ, Ctr Environm Med
    Univ Tokyo, Grad Sch Med, Dept Mol Prevent Med
    Tokushima Bunri Univ, Fac Sci & Engn
    關鍵字: cyclin D1
    hepatocellular carcinoma (HCC)
    日期: 2016-06
    上傳時間: 2018-01-18 11:39:13 (UTC+8)
    出版者: Impact Journals Llc
    摘要: Intestine-specific homeobox (ISX), a newly identified proto-oncogene, is involved in cell proliferation and progression of hepatocellular carcinoma (HCC). However, the underlying mechanisms linking gene expression and tumor formation remain unclear. In this study, we found that ISX transcriptionally activated E2F transcription factor 1 (E2F1) and associated oncogenic activity by directly binding to the E2 site of its promoter. Forced expression of ISX increased the expression of and phosphorylated the serine residue at position 332 of E2F1, which may be translocated into the nucleus to form the E2F1-DP-1 complex, suggesting that the promotion of oncogenic activities of the ISX-E2F1 axis plays a critical role in hepatoma cells. Coexpression of ISX and E2F1 significantly promoted p53 and RB-mediated cell proliferation and anti-apoptosis, and repressed apoptosis and autophagy. In contrast, short hairpin RNAi-mediated attenuation of ISX and E2F1 decreased cell proliferation and malignant transformation, respectively, in hepatoma cells in vitro and in vivo. The mRNA expression of E2F1 and ISX in 238 paired specimens from human HCC patients, and the adjacent, normal tissues exhibited a tumor-specific expression pattern which was highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. Therefore, our results indicate that E2F1 is an important downstream gene of ISX in hepatoma progression.
    關聯: Oncotarget, v.7 n.24, pp.36924-36939
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