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https://ir.cnu.edu.tw/handle/310902800/30984
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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
DP1
E2F1
hepatocellular carcinoma (HCC)
ISX
activation |
| 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 |
| 顯示於類別: | [高齡福祉養生管理系] 期刊論文
[ 食品科技系 ] 期刊論文
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