LILRB1 enhances the progression of diffuse large B-cell lymphoma through the CREB-SORBS3 pathway.

IF 4.8 2区医学 Q2 CELL BIOLOGY

Cellular Oncology Pub Date : 2025-08-01 Epub Date: 2025-05-07 DOI:10.1007/s13402-025-01060-x

Liyuan Cao, Hanqing Zhao, Xuanyi Zhou, Jin Yuan, Lietao Weng, Zhuo Yu, Junke Zheng, Chiqi Chen

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引用次数: 0

Abstract

Purpose: Although 60-70% of diffuse large B-cell lymphoma (DLBCL) patients can be cured with the current standard of chemotherapy and immunotherapy, the remaining patients experience treatment resistance and have poor clinical outcomes. More effective strategies are needed for the DLBCL treatment.

Methods: Databases of clinical patients were analyzed to investigate potential functions of leukocyte immunoglobulin-like receptor B1 (LILRB1) in DLBCL. Short hairpin RNAs were used for validation of in vitro and in vivo function of LILRB1 in DLBCL. RNA-seq was applied to explore potential mechanism, western blot and chromatin immunoprecipitation techniques were used to characterize the underlying signaling of CREB-SORBS3 pathway.

Results: We found that LILRB1 was highly expressed in DLBCL cells and was adversely correlated with the overall survival of DLBCL patients. Knockdown of LILRB1 effectively inhibited the proliferation of DLBCL cells both in vitro and in vivo. Mechanistically, LILRB1 upregulated CREB/CREB phosphorylation and transactivated SORBS3 expression to maintain DLBCL cell proliferation and tumorigenicity.

Conclusion: In this work, we revealed that LILRB1 was highly expressed in DLBCL cells and was negatively correlated with patient survival. Furthermore, we found that the LILRB1-CREB-SORBS3 pathway played a role in maintaining the proliferation of DLBCL cells. These data suggest that LILRB1 might be a potential target for the treatment of DLBCL.

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LILRB1通过CREB-SORBS3途径促进弥漫性大b细胞淋巴瘤的进展。

目的：虽然60-70%的弥漫性大b细胞淋巴瘤（DLBCL）患者在目前的化疗和免疫治疗标准下可以治愈，但其余患者出现治疗耐药，临床预后较差。DLBCL的治疗需要更有效的策略。方法：分析临床患者数据库，探讨白细胞免疫球蛋白样受体B1 （LILRB1）在DLBCL中的潜在功能。利用短发夹rna验证了LILRB1在DLBCL中的体内和体外功能。采用RNA-seq技术探索其潜在机制，采用western blot和染色质免疫沉淀技术表征CREB-SORBS3通路的潜在信号。结果：我们发现LILRB1在DLBCL细胞中高表达，并与DLBCL患者的总生存率呈负相关。在体内和体外，敲低LILRB1可有效抑制DLBCL细胞的增殖。从机制上讲，LILRB1上调CREB/CREB磷酸化，并反激活SORBS3表达，以维持DLBCL细胞的增殖和致瘤性。结论：在本研究中，我们发现LILRB1在DLBCL细胞中高表达，并与患者生存呈负相关。此外，我们发现LILRB1-CREB-SORBS3通路在维持DLBCL细胞的增殖中发挥作用。这些数据表明，LILRB1可能是治疗DLBCL的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.