Suppression of DLBCL Progression by the E3 Ligase Trim35 Is Mediated by CLOCK Degradation and NK Cell Infiltration.
Suppression of DLBCL Progression by the E3 Ligase Trim35 Is Mediated by CLOCK Degradation and NK Cell Infiltration.
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E3 连接酶 Trim35 通过时钟降解和 NK 细胞浸润介导抑制 DLBCL 进展
DOI：
10.1155/2021/9995869
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发表时间：
2021
影响因子：
4.1
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Tan X;Cao F;Tang F;Lu C;Yu Q;Feng S;Yang Z;Chen S;He X;He J;Weng L;Sun L
大多数弥漫性大B细胞淋巴瘤（DLBCL）患者在接受标准的鲁索替尼、环磷酰胺、多柔比星、长春新碱和泼尼松（R - CHOP）化疗后会出现复发或难治性疾病，这在一定程度上与肿瘤免疫微环境失调有关。然而，对于免疫细胞浸润如何得到适当调节，人们知之甚少。在此，我们发现E3泛素连接酶Trim35在人DLBCL组织中低水平表达。我们还表明，Trim35的过表达抑制DLBCL细胞增殖，并且与DLBCL患者的不良生存相关。我们的机制研究表明，Trim35作为一种E3连接酶，介导生物钟节律的关键调节因子CLOCK的泛素化和降解。Trim35的高表达与DLBCL中的自然杀伤（NK）细胞浸润相关，部分原因是CLOCK的降解。一致地，CLOCK高表达的患者总体生存率较差。总体而言，这些发现表明Trim35通过调节肿瘤免疫微环境抑制DLBCL的进展，这意味着它可能是DLBCL中一种有前景的诊断和预后生物标志物。
The majority of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed or refractory disease after standard ruxolitinib, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, which is partly related to a dysregulated tumor immune microenvironment. However, how the infiltration of immune cells is appropriately regulated is poorly understood. Herein, we show that the E3 ubiquitin ligase Trim35 is expressed at low levels in human DLBCL tissues. We also show that overexpression of Trim35 suppresses DLBCL cell proliferation and correlates with inferior survival in DLBCL patients. Our mechanistic study shows that Trim35 functions as an E3 ligase to mediate the ubiquitination and degradation of CLOCK, a key regulator of circadian rhythmicity. High expression of Trim35 correlates with NK cell infiltration in DLBCL, partly due to the degradation of CLOCK. Consistently, patients with high expression of CLOCK show poor overall survival. Overall, these findings suggest that Trim35 suppresses the progression of DLBCL by modulating the tumor immune microenvironment, indicating that it may be a promising diagnostic and prognostic biomarker in DLBCL.
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影响因子：
13.9
作者：
Mohawk JA;Green CB;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
CRL3-SPOP 泛素连接酶复合物通过负调节 MyD88/NF-kappa B 信号传导抑制弥漫性大 B 细胞淋巴瘤的生长
影响因子：
11.4
作者：
Jin, Xiaofeng;Shi, Qing;Wang, Chenji
通讯作者：
Wang, Chenji
影响因子：
20.3
作者：
Hans, CP;Weisenburger, DD;Chan, WC
通讯作者：
Chan, WC