Kong Xiang-pan, Yao Jie, Luo Wei, Feng Fu-kui, Ma Jun-tao, Ren Yi-peng, Wang De-li, Bu Rong-fa
Department of Stomatology, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, 10086, China,
Mol Cell Biochem. 2014 Sep;394(1-2):177-86. doi: 10.1007/s11010-014-2093-4. Epub 2014 Jun 3.
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".
叉头框C1（FOXC1）基因在多种恶性肿瘤中过表达，且与肿瘤进展在功能上相关。然而，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，许多长链非编码RNA（lncRNA）与相邻的编码基因协同作用，形成功能性的“lncRNA- mRNA对”。在本研究中，我们报道了一种新的lncRNA，即FOXC1上游转录本（FOXCUT），它在23例OSCC患者中显著过表达，相邻的FOXC1基因也是如此。FOXC1和FOXCUT的表达呈正相关。当通过小干扰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，通过siRNA下调FOXC1或FOXCUT均可在体外抑制细胞增殖和细胞迁移，并伴随着MMP2、MMP7、MMP9和VEGF-A的减少。总之，在OSCC中FOXC1可能与FOXCUT共同扩增，且它们在功能上均可能参与OSCC的肿瘤进展。这为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点提供了证据。
