Intestine-specific homeobox (ISX) upregulates E2F1 expression and related oncogenic activities in HCC

doi:10.18632/oncotarget.9228

CNU IR > Pharmacy and Science > Dept. of Food Science & Technology > Periodical Articles > Item 310902800/30984

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/30984

Title:	Intestine-specific homeobox (ISX) upregulates E2F1 expression and related oncogenic activities in HCC
Authors:	Wang, Shen-Nien Wang, Li-Ting Sun, Ding-Ping Chai, Chee-Yin Hsi, Edward Kuo, Hsing-Tao Yokoyama, Kazunari K. Hsu, Shih-Hsien
Contributors:	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
Keywords:	cyclin D1 DP1 E2F1 hepatocellular carcinoma (HCC) ISX activation
Date:	2016-06
Issue Date:	2018-01-18 11:39:13 (UTC+8)
Publisher:	Impact Journals Llc
Abstract:	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.
Relation:	Oncotarget, v.7 n.24, pp.36924-36939
Appears in Collections:	[Dept. of Senior Service and Health Management] Periodical Articles [Dept. of Food Science & Technology] Periodical Articles

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