The Silencing of Pokemon Attenuates the Proliferation of Hepatocellular Carcinoma Cells In Vitro and In Vivo by Inhibiting the PI3K/Akt Pathway

被引:29
作者
Lin, Chan-Chan [1 ]
Zhou, Jing-Ping [1 ]
Liu, Yun-Peng [1 ]
Liu, Jing-Jing [1 ]
Yang, Xiao-Ning [1 ]
Jazag, Amarsanaa [3 ]
Zhang, Zhi-Ping [1 ]
Guleng, Bayasi [1 ,2 ]
Ren, Jian-Lin [1 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen, Peoples R China
[2] Xiamen Univ, Coll Med, Fac Clin Med, Xiamen, Peoples R China
[3] 3rd Gen Hosp, Natl Inst Med Res, Ulaanbaatar, Mongolia
来源
PLOS ONE | 2012年 / 7卷 / 12期
基金
中国国家自然科学基金;
关键词
REPRESSES TRANSCRIPTION; NUCLEAR-LOCALIZATION; POOR-PROGNOSIS; FBI-1; ACTIVATION; GENE; EXPRESSION; GROWTH; ERK; MIGRATION;
D O I
10.1371/journal.pone.0051916
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner.
引用
收藏
页数:8
相关论文
共 26 条
  • [11] Proto-oncogene FBI-1 (Pokemon/ZBTB7A) Represses Transcription of the Tumor Suppressor Rb Gene via Binding Competition with Sp1 and Recruitment of Co-repressors
    Jeon, Bu-Nam
    Yoo, Jung-Yoon
    Choi, Won-Il
    Lee, Choong-Eun
    Yoon, Ho-Geun
    Hur, Man-Wook
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (48) : 33199 - 33210
  • [12] FBI-1 enhances transcription of the nuclear factor-κB (NF-κB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-κB
    Lee, DK
    Kang, JE
    Park, HJ
    Kim, MH
    Yim, TH
    Kim, JM
    Heo, MK
    Kim, KY
    Kwon, HJ
    Hur, MW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (30) : 27783 - 27791
  • [13] POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1
    Lee, DK
    Suh, D
    Edenberg, HJ
    Hur, MW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (30) : 26761 - 26768
  • [14] In vitro scratch assay:: a convenient and inexpensive method for analysis of cell migration in vitro
    Liang, Chun-Chi
    Park, Ann Y.
    Guan, Jun-Lin
    [J]. NATURE PROTOCOLS, 2007, 2 (02) : 329 - 333
  • [15] Hepatocellular carcinoma
    Llovet, JM
    Burroughs, A
    Bruix, J
    [J]. LANCET, 2003, 362 (9399) : 1907 - 1917
  • [16] Molecular Mechanisms Underlying Hepatocellular Carcinoma
    Merle, Philippe
    Trepo, Christian
    [J]. VIRUSES-BASEL, 2009, 1 (03): : 852 - 872
  • [17] U6 promoter-driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells
    Miyagishi, M
    Taira, K
    [J]. NATURE BIOTECHNOLOGY, 2002, 20 (05) : 497 - 500
  • [18] FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein
    Morrison, DJ
    Pendergrast, PS
    Stavropoulos, P
    Colmenares, SU
    Kobayashi, R
    Hernandez, N
    [J]. NUCLEIC ACIDS RESEARCH, 1999, 27 (05) : 1251 - 1262
  • [19] Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma
    Nakanishi, K
    Sakamoto, M
    Yamasaki, S
    Todo, S
    Hirohashi, S
    [J]. CANCER, 2005, 103 (02) : 307 - 312
  • [20] Roy Sanjit K, 2010, J Mol Signal, V5, P10, DOI 10.1186/1750-2187-5-10