Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Ireland.
Eur J Cancer. 2011 Aug;47(12):1908-18. doi: 10.1016/j.ejca.2011.04.012. Epub 2011 May 10.
IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2.
The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined.
The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p<0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p<0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level.
This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment.
IL-20 是 IL-10 家族的多效成员，在皮肤生物学和造血细胞发育中发挥作用。最近，IL-20 通过下调 COX-2 被证明在非小细胞肺癌（NSCLC）中具有潜在的抗血管生成作用。
在一系列切除的新鲜冷冻 NSCLC 肿瘤中检查了 IL-20 及其同源受体（IL-20RA/B 和 IL-22R1）的表达。此外，还在正常支气管上皮细胞和 NSCLC 细胞系中检查了这个家族的表达和表观遗传调控。此外，还检查了 IL-20 对 VEGF 家族成员的影响。
IL-20 和其受体在 NSCLC 中经常失调表达。IL-20RB mRNA 在 NSCLC 肿瘤中显著升高（p<0.01）。IL-20RB 和 IL-22R1 受体的蛋白水平在 NSCLC 患者的肿瘤中显著增加（p<0.01）。发现 IL-20 和其受体通过组蛋白翻译后修饰和 DNA CpG 残基甲基化进行表观遗传调控。此外，用重组 IL-20 处理导致 VEGF 家族成员的 mRNA 水平表达降低。
这些基因家族在 NSCLC 中失调，并受到表观遗传调控。虽然 IL-20 的抗血管生成特性需要进一步澄清，但通过表观遗传手段靶向这个家族可能是肺癌治疗的一种可行的治疗选择。
