Oncogenic Effect of the Novel Fusion Gene VAPA-Rab31 in Lung Adenocarcinoma
Fusion genes have been identified as oncogenes in several solid tumors including lung, colorectal, and stomach cancers. Here, we characterized the fusion gene, VAPA-Rab31, discovered from RNA-sequencing data of a patient with lung adenocarcinoma who did not harbor activating mutations in EGFR, KRAS and ALK. This fusion gene encodes a protein comprising the N-terminal region of vesicle-associated membrane protein (VAMP)-associated protein A (VAPA) fused to the C-terminal region of Ras-related protein 31 (Rab31). Exogenous expression of VAPA-Rab31 in immortalized normal bronchial epithelial cells demonstrated the potential transforming effects of this fusion gene, including increased colony formation and cell proliferation in vitro. Also, enhanced tumorigenicity upon VAPA-Rab31 was confirmed in vivo using a mouse xenograft model. Metastatic tumors were also detected in the liver and lungs of xenografted mice. Overexpression of VAPA-Rab31 upregulated anti-apoptotic protein Bcl-2 and phosphorylated CREB both in cells and xenograft tumors. Reduced apoptosis and increased phosphorylation of CREB and Erk were observed in VAPA-Rab31-overexpressing cells after bortezomib treatment. Elevated Bcl-2 level via activated CREB contributed to the resistance to the bortezomib-induced apoptosis. Our data suggest the oncogenic function of the novel fusion gene VAPA-Rab31 via upregulated Bcl-2 and activated CREB in lung cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
International journal of molecular sciences - 20(2019), 9 vom: 10. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoon, Daseul [VerfasserIn] |
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| Links: |
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| Themen: |
BCL2 protein, human |
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| Anmerkungen: |
Date Completed 03.09.2019 Date Revised 25.02.2020 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms20092309 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM29702129X |
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| 245 | 1 | 0 | |a Oncogenic Effect of the Novel Fusion Gene VAPA-Rab31 in Lung Adenocarcinoma |
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| 520 | |a Fusion genes have been identified as oncogenes in several solid tumors including lung, colorectal, and stomach cancers. Here, we characterized the fusion gene, VAPA-Rab31, discovered from RNA-sequencing data of a patient with lung adenocarcinoma who did not harbor activating mutations in EGFR, KRAS and ALK. This fusion gene encodes a protein comprising the N-terminal region of vesicle-associated membrane protein (VAMP)-associated protein A (VAPA) fused to the C-terminal region of Ras-related protein 31 (Rab31). Exogenous expression of VAPA-Rab31 in immortalized normal bronchial epithelial cells demonstrated the potential transforming effects of this fusion gene, including increased colony formation and cell proliferation in vitro. Also, enhanced tumorigenicity upon VAPA-Rab31 was confirmed in vivo using a mouse xenograft model. Metastatic tumors were also detected in the liver and lungs of xenografted mice. Overexpression of VAPA-Rab31 upregulated anti-apoptotic protein Bcl-2 and phosphorylated CREB both in cells and xenograft tumors. Reduced apoptosis and increased phosphorylation of CREB and Erk were observed in VAPA-Rab31-overexpressing cells after bortezomib treatment. Elevated Bcl-2 level via activated CREB contributed to the resistance to the bortezomib-induced apoptosis. Our data suggest the oncogenic function of the novel fusion gene VAPA-Rab31 via upregulated Bcl-2 and activated CREB in lung cancer | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a gene fusion | |
| 650 | 4 | |a lung adenocarcinoma | |
| 650 | 4 | |a tumorigenicity | |
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| 700 | 1 | |a Kim, Jin-Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Yang-Kyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Kyong-Ah |e verfasserin |4 aut | |
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