摘要
Human fibroblast growth factor 9 (FGF9) is a potent mitogen involved in many physiological processes. Although FGF9 messenger RNA (mRNA) is ubiquitously expressed in embryos, FGF9 protein expression is generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in human malignancies including cancers, but the mechanism remains largely unknown. Here, we report that FGF9 protein, but not mRNA, was increased in hypoxia. Two sequence elements, the upstream open reading frame (uORF) and the internal ribosome entry site (IRES), were identified in the 5' UTR of FGF9 mRNA. Functional assays indicated that FGF9 protein synthesis was normally controlled by uORF-mediated translational repression, which kept the protein at a low level, but was upregulated in response to hypoxia through a switch to IRES-dependent translational control. Our data demonstrate that FGF9 IRES functions as a cellular switch to turn FGF9 protein synthesis 'on' during hypoxia, a likely mechanism underlying FGF9 overexpression in cancer cells. Finally, we provide evidence to show that hypoxia-induced translational activation promotes FGF9 protein expression in colon cancer cells. Altogether, this dynamic working model may provide a new direction in anti-tumor therapies and cancer intervention.
| 原文 | English |
|---|---|
| 頁（從 - 到） | 2932-2944 |
| 頁數 | 13 |
| 期刊 | Nucleic acids research |
| 卷 | 42 |
| 發行號 | 5 |
| DOIs | |
| 出版狀態 | Published - 2014 一月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Genetics
引用此文
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Overexpression of FGF9 in colon cancer cells is mediated by hypoxia-induced translational activation. / Chen, Tsung Ming; Shih, Yu Heng; Tseng, Ta-Chien; Lai, Ming Chih; Wu, Chih Hao; Li, Yi Han; Tsai, Shaw-Jenq; Sun, Hsiao-Fang.
於: Nucleic acids research, 卷 42, 編號 5, 01.01.2014, p. 2932-2944.研究成果: Article
TY - JOUR
T1 - Overexpression of FGF9 in colon cancer cells is mediated by hypoxia-induced translational activation
AU - Chen, Tsung Ming
AU - Shih, Yu Heng
AU - Tseng, Ta-Chien
AU - Lai, Ming Chih
AU - Wu, Chih Hao
AU - Li, Yi Han
AU - Tsai, Shaw-Jenq
AU - Sun, Hsiao-Fang
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Human fibroblast growth factor 9 (FGF9) is a potent mitogen involved in many physiological processes. Although FGF9 messenger RNA (mRNA) is ubiquitously expressed in embryos, FGF9 protein expression is generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in human malignancies including cancers, but the mechanism remains largely unknown. Here, we report that FGF9 protein, but not mRNA, was increased in hypoxia. Two sequence elements, the upstream open reading frame (uORF) and the internal ribosome entry site (IRES), were identified in the 5' UTR of FGF9 mRNA. Functional assays indicated that FGF9 protein synthesis was normally controlled by uORF-mediated translational repression, which kept the protein at a low level, but was upregulated in response to hypoxia through a switch to IRES-dependent translational control. Our data demonstrate that FGF9 IRES functions as a cellular switch to turn FGF9 protein synthesis 'on' during hypoxia, a likely mechanism underlying FGF9 overexpression in cancer cells. Finally, we provide evidence to show that hypoxia-induced translational activation promotes FGF9 protein expression in colon cancer cells. Altogether, this dynamic working model may provide a new direction in anti-tumor therapies and cancer intervention.
AB - Human fibroblast growth factor 9 (FGF9) is a potent mitogen involved in many physiological processes. Although FGF9 messenger RNA (mRNA) is ubiquitously expressed in embryos, FGF9 protein expression is generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in human malignancies including cancers, but the mechanism remains largely unknown. Here, we report that FGF9 protein, but not mRNA, was increased in hypoxia. Two sequence elements, the upstream open reading frame (uORF) and the internal ribosome entry site (IRES), were identified in the 5' UTR of FGF9 mRNA. Functional assays indicated that FGF9 protein synthesis was normally controlled by uORF-mediated translational repression, which kept the protein at a low level, but was upregulated in response to hypoxia through a switch to IRES-dependent translational control. Our data demonstrate that FGF9 IRES functions as a cellular switch to turn FGF9 protein synthesis 'on' during hypoxia, a likely mechanism underlying FGF9 overexpression in cancer cells. Finally, we provide evidence to show that hypoxia-induced translational activation promotes FGF9 protein expression in colon cancer cells. Altogether, this dynamic working model may provide a new direction in anti-tumor therapies and cancer intervention.
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UR - http://www.scopus.com/inward/citedby.url?scp=84899006080&partnerID=8YFLogxK
U2 - 10.1093/nar/gkt1286
DO - 10.1093/nar/gkt1286
M3 - Article
C2 - 24334956
AN - SCOPUS:84899006080
VL - 42
SP - 2932
EP - 2944
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 5
ER -