Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy.
视网膜母细胞瘤（RB）是儿童早期最常见的眼内恶性肿瘤。基因表达谱分析显示，在RB细胞中，胃抑制多肽受体（GIPR）在三叶因子家族肽1（TFF1）过表达后上调。本研究发现，这种G蛋白偶联跨膜受体与TFF1共表达，而TFF1是晚期2亚型RB的一种新型诊断和预后生物标志物。在两种RB细胞系中的功能分析表明，通过慢病毒稳定过表达GIPR后，细胞活力和生长显著降低，同时细胞凋亡增加，这与TFF1过表达后观察到的效应一致。在鸡胚绒毛尿囊膜（CAM）实验中，过表达GIPR的RB细胞形成的CAM肿瘤显著减小。GIPR抑制剂MK0893可逆转GIPR过表达在RB细胞中的作用。给予重组TFF1并未增强GIPR过表达效应，表明GIPR并非TFF1的受体。对GIPR潜在上下游介导因子的研究提示，miR-542-5p和p53可能参与GIPR信号传导。我们的研究结果表明GIPR在RB中具有肿瘤抑制作用，提示其信号通路可能成为未来视网膜母细胞瘤治疗的新潜在靶点。
肿瘤(癌症)患者之家