A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis
BACKGROUND: Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated.
METHODS: Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed.
RESULTS: In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments.
CONCLUSIONS: Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:124 |
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| Enthalten in: |
British journal of cancer - 124(2021), 1 vom: 17. Jan., Seite 290-298 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bae, Kieun [VerfasserIn] |
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| Links: |
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| Themen: |
BCAR4 non-coding RNA, human |
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| Anmerkungen: |
Date Completed 20.04.2021 Date Revised 07.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41416-020-01146-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317712659 |
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| 100 | 1 | |a Bae, Kieun |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Revised 07.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated | ||
| 520 | |a METHODS: Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed | ||
| 520 | |a RESULTS: In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments | ||
| 520 | |a CONCLUSIONS: Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a BCAR4 non-coding RNA, human |2 NLM | |
| 650 | 7 | |a CD63 protein, human |2 NLM | |
| 650 | 7 | |a Oncogene Proteins, Fusion |2 NLM | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a Tetraspanin 30 |2 NLM | |
| 700 | 1 | |a Kim, Jin Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Hyojik |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Sun-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yun-Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sunshin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Geon Kook |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jin Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jake June-Koo |e verfasserin |4 aut | |
| 700 | 1 | |a Ju, Young Seok |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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