SCUBE3 exerts a tumor-promoting effect in tongue squamous cell carcinoma by promoting CEBPA binding to the CCL2 promoter
Tongue squamous cell carcinoma (TSCC) is the main pathological subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration and invasion, induced apoptosis as well as cell cycle arrest in G2 phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, signal transducer and activator of transcription 3 (STAT3) signaling contributed to CCL2-mediated phenotypes in TSCC cells. Implications: our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/ CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Molecular cancer research : MCR - (2024) vom: 13. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Minhui [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 13.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1158/1541-7786.MCR-23-0038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368398641 |
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| 100 | 1 | |a Zhu, Minhui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SCUBE3 exerts a tumor-promoting effect in tongue squamous cell carcinoma by promoting CEBPA binding to the CCL2 promoter |
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| 500 | |a Date Revised 13.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Tongue squamous cell carcinoma (TSCC) is the main pathological subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration and invasion, induced apoptosis as well as cell cycle arrest in G2 phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, signal transducer and activator of transcription 3 (STAT3) signaling contributed to CCL2-mediated phenotypes in TSCC cells. Implications: our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/ CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Ma, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shicai |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiaoqiong |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Hongsen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Fangfei |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Hongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Caiyun |e verfasserin |4 aut | |
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