背景:恶性黑色素瘤是一种罕见的人类和动物癌症,不仅发生在皮肤中,也发生在鼻子的粘膜中,嘴,肛门,消化道,在眼睛的葡萄膜(脉络膜)。为了开发治疗方法,我们需要更好地了解基因景观和信号通路。大量研究强调了NKG2A-HLA-E在肿瘤免疫治疗中的重要性。但HLA-E在肿瘤细胞中的功能和机制很少单独研究。来自可公开获得的数据库Oncomine和癌症基因组图谱(TCGA)的统计分析显示,与未转化的对应物相比,HLA-E在黑素瘤中高度表达。此外,HLA-E高表达的黑色素瘤患者的OS率低于低表达的患者。这些数据表明HLA-E在人黑素瘤中的重要性。Qa-1b是小鼠HLA-E的同源物。
目的:探讨Qa-1b在小鼠黑色素瘤中的作用及机制。
方法:用小鼠黑色素瘤细胞株B16-F10和同种异体黑色素瘤模型研究Qa-1b在黑色素瘤中的作用及机制。
结果:与正常小鼠表皮细胞相比,Qa-1b在B16-F10中高表达。Qa-1b敲低抑制B16-F10细胞的体外增殖和迁移以及体内同种异体黑色素瘤过程。此外,Qa-1b敲低通过Ras-Raf-MAPK信号通路促进G0/G1期细胞周期阻滞和细胞凋亡。
结论:Qa-1b具有致癌因子的作用,可作为黑色素瘤新的治疗靶点。
BACKGROUND: Malignant melanoma is one kind of rare cancer in human and animals, which occurs not only in skin but also in the mucous membranes of the nose, mouth, anus, digestive tract, and in the uvea (choroid) of the eye. In order to develop therapies, a better understanding of the genetic landscape and signal pathways are needed. Numerous studies highlighted the importance of NKG2A-HLA-E in tumor immunotherapy, but the function and mechanism of HLA-E in tumor cells have seldom been studied alone. The statistical analyses from publicly available database Oncomine and The Cancer Genome Atlas (TCGA) showed that HLA-E is highly expressed in melanoma compared to non-transformed counterparts. In addition, melanoma patients with HLA-E high expression had a worse OS rate than the patients with low expression. These data indicate the importance of HLA-E in human melanoma. Qa-1b is the homolog of HLA-E in mouse.
OBJECTIVE: To investigate the function and mechanism of Qa-1b in mouse melanoma.
METHODS: Mouse melanoma cell line B16-F10 and allogenic melanoma model were used to investigate the function and mechanism of Qa-1b in melanoma.
RESULTS: Qa-1b was highly expressed in B16-F10 compared with normal mouse epidermal cells. Qa-1b knockdown inhibited B16-F10 cell proliferation and migration in vitro and allogenic melanoma process in vivo. Furthermore, Qa-1b knockdown promoted cell cycle arrest at G0/G1 phase and cell apoptosis through Ras-Raf-MAPK signal pathway.
CONCLUSIONS: Qa-1b functions as an oncogenic factor and it can be used as a new therapeutic target in melanoma.