LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer
| Autor: | Peng Cui, Jing Wu, Jing Zhao, Peizhun Du, Yunyun Qin, Lun-Xiu Qin, Wenhong Zhang, Zhongwen Zhou, Cheng’en Hu, Guangjian Huang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor Vascular Endothelial Growth Factor A Cancer Research Angiogenesis Carcinogenesis Mice Nude Biology Cell Line Neovascularization 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Stomach Neoplasms Cell Line Tumor Genetics medicine Human Umbilical Vein Endothelial Cells Animals Humans STAT3 Promoter Regions Genetic Molecular Biology Cell Proliferation Regulation of gene expression Neovascularization Pathologic Hedgehog signaling pathway PVT1 Up-Regulation Gene Expression Regulation Neoplastic Vascular endothelial growth factor A 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein RNA Long Noncoding medicine.symptom Signal Transduction |
| Zdroj: | Oncogene. 37(30) |
| ISSN: | 1476-5594 |
| Popis: | Angiogenesis can aggravate gastric cancer progression. LncRNAs exert important roles in regulating various cancer behaviors. However, the functions and mechanisms of lncRNAs in angiogenesis remain largely unknown. Here we demonstrated that lncRNA PVT1 was upregulated and significantly associated with high-microvessel density and poor prognosis in gastric cancer. Through gain- and loss-of PVT1 expression, we found PVT1 could obviously induce angiogenesis within tumors, in addition to promoting tumor growth in vitro and in vivo. Mechanistically, PVT1 directly interacted with the signal transducer activator phospho-STAT3 in the nucleus, and increased its protein stability by protecting it from poly-ubiquitination and proteasome-dependent degradation. The binding of PVT1 activated the STAT3 signalling pathway, and successively elevated VEGFA expression to stimulate angiogenesis. The positive correlation of PVT1 and VEGFA expression was also verified in gastric cancer specimens, and high levels of PVT1 and VEGFA in combination frequently predicted shorter survival time. Moreover, we revealed that PVT1 was a STAT3-responsive lncRNA, as STAT3 could occupy the PVT1 promoter to facilitate its transcription. The positive feed-back loop of PVT1 and STAT3 continuously enhanced the oncogenic effects. Collectively, our study first elucidates the mechanism of PVT1-mediated angiogenesis via evoking the STAT3/VEGFA signalling axis, which provides promising target for developing new therapeutic strategy in gastric cancer. |
| Databáze: | OpenAIRE |
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