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The expression and functional role of a FOXC1 related mRNA-lncRNA pair in oral squamous cell carcinoma

机译:FOXC1相关mRNA-lncRNA对在口腔鳞癌中的表达及其功能

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摘要

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”.
机译:叉头箱C1(FOXC1)基因在多种恶性肿瘤中过表达,并且在功能上与肿瘤进展相关。但是,其在口腔鳞状细胞癌(OSCC)中的作用仍不清楚。最近的研究表明,许多长的非编码RNA(lncRNA)与相邻的编码基因合作,形成了功能性的“ lncRNA-mRNA对”。在这项研究中,我们报告了一个新的lncRNA FOXC1上游转录本(FOXCUT),与邻近的FOXC1基因一样,在23例OSCC患者中明显过表达。 FOXC1和FOXCUT的表达呈正相关。当小干扰RNA(siRNA)下调FOXCUT的表达时,FOXC1的表达也降低。此外,在OSCC细胞Tca8113和SCC-9中,siRNA对FOXC1或FOXCUT的下调可以抑制体外细胞增殖和细胞迁移,并伴有MMP2,MMP7,MMP9和VEGF-A的降低。总之,在OSCC中FOXC1可以与FOXCUT共同扩增,并且两者都可能在功能上参与OSCC的肿瘤进展。这提供了证据,即FOXC1和FOXCUT均可作为过表达这种“ lncRNA-mRNA对”的OSCC患者的新型生物标志物和治疗靶标。

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