Jiang Lei, Xu Yulian, Zeng Xinli, Fang Jianchen, Morse Herbert C, Zhou Jeff X
Department of Pathology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
Department of ENT, Ningbo Second People's Hospital, Ningbo, China.
Oncotarget. 2015 Oct 13;6(31):31191-202. doi: 10.18632/oncotarget.5152.
CD300A is a type I transmembrane receptor protein which has shown inhibitory effects on B-cell receptor-mediated signals. In an analysis of public dataset, we found that CD300A mRNA levels were inversely correlated with the overall survival time of patients with diffuse large B-cell lymphoma (DLBCL). To decipher the role of CD300A in DLBCL, we knocked down the expression levels of CD300A in DLBCL cells and found that decreasing levels of CD300A significantly inhibited cell proliferation of OCI-Ly01, Farage, and SUDHL-4 cells, but not of VAL, OCI-Ly10, or SUDHL-8 cells. Mechanistically, reduced expression of CD300A resulted in a marked attenuation of AKT phosphorylation, a key molecular event in tumorigenesis, in OCI-Ly01, Farage, and SUDHL-4 cells. Pharmacologic inhibition of PI3K displayed a similar inhibitory effect on cell proliferation. Furthermore, using a xenograft animal model, we found that decreasing levels of CD300A in OCI-Ly01 and Farage cells significantly inhibited tumor formation in vivo. Collectively, our results suggested an oncogenic role of CD300A in DLBCL which could serve as a potential biomarker and therapeutic target for this malignant disease.
CD300A是一种I型跨膜受体蛋白,已显示出对B细胞受体介导的信号具有抑制作用。在对公共数据集的分析中,我们发现CD300A mRNA水平与弥漫性大B细胞淋巴瘤(DLBCL)患者的总生存时间呈负相关。为了解析CD300A在DLBCL中的作用,我们敲低了DLBCL细胞中CD300A的表达水平,发现CD300A水平的降低显著抑制了OCI-Ly01、Farage和SUDHL-4细胞的增殖,但对VAL、OCI-Ly10或SUDHL-8细胞没有抑制作用。从机制上讲,CD300A表达的降低导致OCI-Ly01、Farage和SUDHL-4细胞中AKT磷酸化显著减弱,AKT磷酸化是肿瘤发生中的关键分子事件。PI3K的药理学抑制对细胞增殖显示出类似的抑制作用。此外,使用异种移植动物模型,我们发现OCI-Ly01和Farage细胞中CD300A水平的降低显著抑制了体内肿瘤的形成。总体而言,我们的结果表明CD300A在DLBCL中具有致癌作用,它可能作为这种恶性疾病的潜在生物标志物和治疗靶点。