Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma
Although identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further dem...
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doaj-69e26a1c49bd4a34a514eb05f57a33f22020-11-25T03:48:50ZengWileyMolecular Oncology1574-78911878-02612018-09-011291480149710.1002/1878-0261.12357Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinomaXuejie Min0Jun Wen1Li Zhao2Kaiying Wang3Qingli Li4Gang Huang5Jianjun Liu6Xiaoping Zhao7Department of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaShanghai University of Medicine & Health Sciences ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaDepartment of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University ChinaAlthough identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further demonstrated that the nuclear role of HDGF involved regulation of transcription of lipid metabolism genes. HDGF‐induced expression of lipogenic genes was mainly associated with activation of sterol regulatory element binding protein (SREBP) transcription factor. Coexpression of SREBP‐1 and nuclear HDGF predicts poor prognosis for HCC. In addition, by changing the first amino acid of the PWWP domain from proline to alanine, the type of PWWP domain changed from P‐ to A‐type, resulting in inability to induce SREBP‐1‐mediated gene transcription. The type of PWWP domain affects the recruitment of the C‐terminal binding protein‐1 transcriptional repressor on the promoter of the lipogenic gene. Our data indicate that HDGF acts as a coactivator of SREBP1‐mediated transcription of lipogenic genes. The PWWP domain is crucial for HDGF to promote lipogenesis. Moreover, transcriptional regulation of nuclear HDGF plays important roles in the development of HCC.https://doi.org/10.1002/1878-0261.12357HCCHDGFlipid metabolismSREBP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuejie Min Jun Wen Li Zhao Kaiying Wang Qingli Li Gang Huang Jianjun Liu Xiaoping Zhao |
spellingShingle |
Xuejie Min Jun Wen Li Zhao Kaiying Wang Qingli Li Gang Huang Jianjun Liu Xiaoping Zhao Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma Molecular Oncology HCC HDGF lipid metabolism SREBP |
author_facet |
Xuejie Min Jun Wen Li Zhao Kaiying Wang Qingli Li Gang Huang Jianjun Liu Xiaoping Zhao |
author_sort |
Xuejie Min |
title |
Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
title_short |
Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
title_full |
Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
title_fullStr |
Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
title_full_unstemmed |
Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
title_sort |
role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2018-09-01 |
description |
Although identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further demonstrated that the nuclear role of HDGF involved regulation of transcription of lipid metabolism genes. HDGF‐induced expression of lipogenic genes was mainly associated with activation of sterol regulatory element binding protein (SREBP) transcription factor. Coexpression of SREBP‐1 and nuclear HDGF predicts poor prognosis for HCC. In addition, by changing the first amino acid of the PWWP domain from proline to alanine, the type of PWWP domain changed from P‐ to A‐type, resulting in inability to induce SREBP‐1‐mediated gene transcription. The type of PWWP domain affects the recruitment of the C‐terminal binding protein‐1 transcriptional repressor on the promoter of the lipogenic gene. Our data indicate that HDGF acts as a coactivator of SREBP1‐mediated transcription of lipogenic genes. The PWWP domain is crucial for HDGF to promote lipogenesis. Moreover, transcriptional regulation of nuclear HDGF plays important roles in the development of HCC. |
topic |
HCC HDGF lipid metabolism SREBP |
url |
https://doi.org/10.1002/1878-0261.12357 |
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