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A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors.

Dis Model Mech. 2013 Mar;6(2):414-23. Epub 2012 Oct 04
Zhen Li 1 , Weiling Zheng , Zhengyuan Wang , Zhiqiang Zeng , Huiqing Zhan , Caixia Li , Li Zhou , Chuan Yan , Jan M Spitsbergen , Zhiyuan Gong
Zhen Li 1 , Weiling Zheng , Zhengyuan Wang , Zhiqiang Zeng , Huiqing Zhan , Caixia Li , Li Zhou , Chuan Yan , Jan M Spitsbergen , Zhiyuan Gong
+ et al

[No authors listed]

Author information
  • 1 Department of Biological Sciences, National University of Singapore, Singapore.
全文

摘要


Myc is a pleiotropic transcription factor that is involved in many cellular activities relevant to carcinogenesis, including hepatocarcinogenesis. The zebrafish has been increasingly used to model human diseases and it is particularly valuable in helping to identify common and conserved molecular mechanisms in vertebrates. Here we generated a liver tumor model in transgenic zebrafish by liver-specific expression of mouse Myc using a Tet-On system. Dosage-dependent induction of Myc expression specifically in the liver was observed in our Myc transgenic zebrafish, TO(Myc), and the elevated Myc expression caused liver hyperplasia, which progressed to hepatocellular adenoma and carcinoma with prolonged induction. Next generation sequencing-based transcriptomic analyses indicated that ribosome proteins were overwhelmingly upregulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human those of hepatocellular carcinoma. Finally, we found that a small Myc target gene set of 16 genes could be used to identify liver tumors due to Myc upregulation. Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
GEO Accessiongenotypetissuetreatment
GSM1000561: M+D+_2
Danio rerio GSM1000561: M+D+_2; Danio rerio; RNA-Seq RNA-Seq AB SOLiD 3 Plus System GSM1000561 Tg(fabp10:TA; TRE:Myc; krt4:GFP) liver doxycycline
GSM1000560: M+D+_1
Danio rerio GSM1000560: M+D+_1; Danio rerio; RNA-Seq RNA-Seq AB SOLiD 3 Plus System GSM1000560 Tg(fabp10:TA; TRE:Myc; krt4:GFP) liver doxycycline
GSM1000559: M-D+_2
Danio rerio GSM1000559: M-D+_2; Danio rerio; RNA-Seq RNA-Seq AB SOLiD 3 Plus System GSM1000559 wildtype liver doxycycline
GSM1000558: M-D+_1
Danio rerio GSM1000558: M-D+_1; Danio rerio; RNA-Seq RNA-Seq AB SOLiD 3 Plus System GSM1000558 wildtype liver doxycycline
GSM1000557: M+D-_2
Danio rerio GSM1000557: M+D-_2; Danio rerio; RNA-Seq RNA-Seq AB SOLiD 3 Plus System GSM1000557 Tg(fabp10:TA; TRE:Myc; krt4:GFP) liver none