Suppression of CD300A inhibits the growth of diffuse large B-cell lymphoma.
Suppression of CD300A inhibits the growth of diffuse large B-cell lymphoma.
复制标题
抑制 CD300A 可抑制弥漫性大 B 细胞淋巴瘤的生长。
DOI：
10.18632/oncotarget.5152
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Zhou JX
中科院分区：
文献类型：
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作者：
Jiang L;Xu Y;Zeng X;Fang J;Morse HC 3rd;Zhou JX
CD300A是一种I型跨膜受体蛋白，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。为了解释CD300A在DLBCL中的作用，我们降低了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，而对VAL、OCI-Ly10和SUDHL-8细胞的增殖没有作用。在OCI-Ly01、Farage和SUDHL-4细胞中，CD300A表达的降低导致AKT磷酸化的显著衰减，AKT磷酸化是肿瘤发生的关键分子事件。药理抑制PI3K对细胞增殖也有类似的抑制作用。此外，通过异种移植动物模型，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。总之，我们的研究结果表明CD300A在DLBCL中的致癌作用，可以作为这种恶性疾病的潜在生物标志物和治疗靶点。
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.