The critical role of RasGRP4 in the growth of diffuse large B cell lymphoma
The critical role of RasGRP4 in the growth of diffuse large B cell lymphoma
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RasGRP4 在弥漫性大 B 细胞淋巴瘤生长中的关键作用
DOI：
10.1186/s12964-019-0415-6
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发表时间：
2019-08
影响因子：
8.4
通讯作者：
Yu Hong
中科院分区：
文献类型：
--
作者：
Zhu Lin;Xia Chunyan;Wu Lin;Zhang Yuxuan;Liu Junling;Chen Yinan;Liu Jing;Xiao Yongxin;Nie Kai;Huang Liyu;Qu Ning;Yu Hong
本研究旨在证实阻断RasGRP4在体外和体内均能有效减缓DLBCL的生长，并明确RasGRP4在临床DLBCL预后中的作用。方法检测srasgrp4在良性组织和淋巴瘤组织中的表达水平。为了验证RasGRP4基因的体细胞突变，我们对DLBCL患者进行了cDNA测序。通过敲低RasGRP4，检测细胞增殖、线粒体膜电位、氧化应激水平和信号通路变化。观察异种移植淋巴瘤模型的肿瘤生长情况。收集临床资料以证实RasGRP4在DLBCL中的作用。结果rasgrp4在DLBCL中表达显著升高，而在DLBCL患者中未检测到该基因的体细胞突变。降低的RasGRP4通过减少有丝分裂和促进细胞凋亡同时抑制细胞增殖，增加氧化应激水平。在SUDHL-4细胞中，RasGRP4表达的降低降低了ERK的表达，同时增加了JNK的表达。在体内，敲低RasGRP4也能显著抑制肿瘤的形成。此外，RasGRP4在DLBCL病变较大的患者（P= 0.0004）、国际预后指数评分高危组（P= 0.0042）中表达水平明显较高，且其表达与DLBCL中最大标准化摄取值呈正相关（P= 0.0004）。结论这些发现提示RasGRP4在DLBCL中的致癌作用，提示其作为DLBCL的预后生物标志物和潜在的治疗靶点。
BackgroundThis study aimed to confirm that blocking RasGRP4 can effectively slow down the growth of DLBCL both in vitro and in vivo and ascertain the role of RasGRP4 in the prognosis of DLBCL clinically.MethodsRasGRP4 expression levels were examined in benign tissues and lymphomas. In order to verify somatic mutation in RasGRP4 gene, cDNA sequencing was performed in DLBCL patients. RasGRP4-dependent cell proliferation, mitochondrial membrane potential, oxidative stress levels and signaling pathway changes were measured by knockdown of RasGRP4. Tumor growth was monitored in xenografted lymphoma model. Clinical data were collected to confirm the role of RasGRP4 in DLBCL.ResultsRasGRP4 expression was significantly elevated in DLBCL while no somatic mutations were detected of this gene in DLBCL patients. Decreased RasGRP4 significantly inhibited cell proliferation by simultaneously reducing mitosis and promoting apoptosis and increased the oxidative stress levels. Mechanistically, reduced expression of RasGRP4 decreased ERK while increased JNK expression in SUDHL-4 cells. Knockdown of RasGRP4 also significantly inhibited tumor formation in vivo. Furthermore, RasGRP4 expression levels were significantly higher in patients with larger DLBCL lesions (P= 0.0004), high-risk international prognostic index score groups (P= 0.0042), and its expression was positively correlated with maximum standardized uptake value in DLBCL (P= 0.0004).ConclusionsThese findings indicate the oncogenic role of RasGRP4 in DLBCL, suggesting it as a prognostic biomarker and potential therapeutic target in DLBCL.
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影响因子：
5.3
作者：
通讯作者：
--
影响因子：
3.8
作者：
Vega GG;Avilés-Salas A;Chalapud JR;Martinez-Paniagua M;Pelayo R;Mayani H;Hernandez-Pando R;Martinez-Maza O;Huerta-Yepez S;Bonavida B;Vega MI
通讯作者：
Vega MI
影响因子：
11.2
作者：
P. Lorenzo;Justin W. Kung;D. Bottorff;S. Garfield;James C. Stone;P. M. Blumberg
通讯作者：
P. Lorenzo;Justin W. Kung;D. Bottorff;S. Garfield;James C. Stone;P. M. Blumberg
在第三阶段和IV弥漫大型B细胞淋巴瘤中，仅基于利妥昔单抗化疗后局部复发的预测因素：巩固辐射的指导决定。
DOI：
10.1016/j.ijrobp.2015.01.025
发表时间：
2015-05-01
影响因子：
7
作者：
Jegadeesh, Naresh;Rajpara, Raj;Esiashvili, Natia;Shi, Zheng;Liu, Yuan;Okwan-Duodu, Derrick;Flowers, Christopher R.;Khan, Mohammad K.
通讯作者：
Khan, Mohammad K.
影响因子：
11.2
作者：
Dai B;Zhao XF;Hagner P;Shapiro P;Mazan-Mamczarz K;Zhao S;Natkunam Y;Gartenhaus RB
通讯作者：
Gartenhaus RB