Abstract
The Fork head box C1 (FOXC1) gene is overexpressed in multiple malignant tumors and is functionally correlated with tumor progression. However, its' role in oral squamous cell carcinoma (OSCC) is still unclear. Recent studies have revealed that many long non-coding RNA (lncRNAs) cooperate with adjacent coding genes and form a functional "lncRNA-mRNA pair". In this study, we report a new lncRNA FOXC1 upstream transcript (FOXCUT) that was remarkably overexpressed in 23 OSCC patients, as was the adjacent FOXC1 gene. The expressions of FOXC1 and FOXCUT were positively correlated. When the expression of FOXCUT was down-regulated by small interfering RNA (siRNA), the expression of FOXC1 was also decreased. Moreover, in OSCC cells Tca8113 and SCC-9, down-regulation of either FOXC1 or FOXCUT by siRNA could inhibit cell proliferation and cell migration in vitro and was accompanied with a reduction of MMP2, MMP7, MMP9, and VEGF-A. In conclusion, FOXC1 may be co-amplified with FOXCUT in OSCC, and both of them may be functionally involved in the tumor progression of OSCC. This provides evidence that both FOXC1 and FOXCUT may serve as novel biomarkers and therapeutic targets in OSCC patients who overexpress this "lncRNA-mRNA pair".
MeSH terms
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Forkhead Transcription Factors / genetics*
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation, Neoplastic
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Head and Neck Neoplasms / genetics*
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Head and Neck Neoplasms / metabolism
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Head and Neck Neoplasms / pathology
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Humans
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 7 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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Mouth Neoplasms / genetics*
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Mouth Neoplasms / metabolism
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Mouth Neoplasms / pathology
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Neoplasm Invasiveness
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RNA Interference
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RNA, Long Noncoding / genetics*
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RNA, Long Noncoding / metabolism
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RNA, Messenger / genetics*
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RNA, Messenger / metabolism
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Squamous Cell Carcinoma of Head and Neck
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Time Factors
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Transfection
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Up-Regulation
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Biomarkers, Tumor
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FOXC1 protein, human
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Forkhead Transcription Factors
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RNA, Long Noncoding
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RNA, Messenger
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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long non-coding RNA FOXCUT, human
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MMP7 protein, human
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Matrix Metalloproteinase 7
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MMP2 protein, human
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Matrix Metalloproteinase 2
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MMP9 protein, human
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Matrix Metalloproteinase 9