Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, CMN-SXXI. IMSS, CDMX, Mexico.
Departamento de Biomedicina Molecular, CINVESTAV, CDMX, Mexico.
Sci Rep. 2018 Jun 21;8(1):9445. doi: 10.1038/s41598-018-27711-8.
Cervical cancer (CC) is associated with alterations in immune system balance, which is primarily due to a shift from Th1 to Th2 and the unbalance of Th17/Treg cells. Using in silico DNA copy number analysis, we have demonstrated that ~20% of CC samples exhibit gain of 8q22.3 and 19q13.31; the regions of the genome that encodes the KLF10 and PSG genes, respectively. Gene expression studies demonstrated that there were no alterations in KLF10 mRNA expression, whilst the PSG2 and -5 genes were up-regulated by 1.76 and 3.97-fold respectively in CC compared to normal tissue controls. siRNA and ChIP experiments in SiHa cells have demonstrated that KLF10 participates in immune response through regulation of IL6, IL25 and PSG2 and PSG5 genes. Using cervical tissues from KLF10 mice, we have identified down-regulation of PSG17, -21 and -23 and IL11. These results suggest that KLF10 may regulate immune system response genes in cervical cancer among other functions. KLF10 and PSG copy number variations and alterations in mRNA expression levels could represent novel molecular markers in CC.
宫颈癌(CC)与免疫系统平衡的改变有关,这主要是由于 Th1 向 Th2 的转变以及 Th17/Treg 细胞的失衡。通过计算机 DNA 拷贝数分析,我们已经证明大约 20%的 CC 样本表现出 8q22.3 和 19q13.31 的增益;分别编码 KLF10 和 PSG 基因的基因组区域。基因表达研究表明 KLF10 mRNA 表达没有改变,而 PSG2 和-5 基因在 CC 中相对于正常组织对照分别上调了 1.76 倍和 3.97 倍。SiHa 细胞中的 siRNA 和 ChIP 实验表明,KLF10 通过调节 IL6、IL25 和 PSG2 和 PSG5 基因参与免疫反应。使用 KLF10 小鼠的宫颈组织,我们鉴定出 PSG17、-21 和-23 和 IL11 的下调。这些结果表明,KLF10 可能在其他功能中调节宫颈癌中的免疫系统反应基因。KLF10 和 PSG 的拷贝数变化以及 mRNA 表达水平的改变可能是 CC 的新型分子标志物。