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CAPG 通过 PI3K/AKT 信号通路促进弥漫性大 B 细胞淋巴瘤细胞的进展。

CAPG facilitates diffuse large B-cell lymphoma cell progression through PI3K/AKT signaling pathway.

机构信息

Department of Lymphatic Oncology, Cancer Center of Shanxi Bethune Hospital (The Third Hospital of Shanxi Medical University), Taiyuan City, Shanxi Province 030032, China.

Department of Lymphatic Oncology, Cancer Center of Shanxi Bethune Hospital (The Third Hospital of Shanxi Medical University), Taiyuan City, Shanxi Province 030032, China.

出版信息

Hum Immunol. 2022 Dec;83(12):832-842. doi: 10.1016/j.humimm.2022.10.001. Epub 2022 Oct 14.

Abstract

OBJECTIVE

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous tumor. Currently, macrophage-capping protein (CAPG) has been discovered to play a crucial part as a regulator in various cancers. However, it still remains unclear regarding its regulatory mechanism in DLBCL. Therefore, this study focused on revealing the mechanism underlying CAPG in DLBCL.

METHODS

The bioinformatics analysis was conducted to predict the expression of CAPG in DLBCL and its downstream target genes. qRT-PCR was utilized to detect mRNA expression levels of CAPG and CEBPA. Western blot was performed to examine the expression levels of related proteins. Then we employed flow cytometry for the analysis of cell cycle and apoptosis. We also used MTT assay to measure cell survival and IHC assay to detect CAPG expression in DLBLC tissues. Then, ChIP was used to determine the binding of CEBPA and CAPG. For in vivo experiments, xenograft models were employed to investigate the effect of CAPG on DLBCL.

RESULTS

High-level of CAPG expression was found in DLBCL cells and tissues. CAPG could strengthen the proliferative and invasive abilities of DLBCL cells, inhibit cell apoptosis, and activate PI3K/AKT signaling pathway. CAPG overexpression accelerated malignant progression of DLBCL cells. In addition, CAPG expression was regulated by CEBPA.

CONCLUSION

CAPG enhances the proliferation and invasion of DLBCL cells by promoting PI3K/AKT signaling pathway, which is expected to be a promising target for DLBCL.

摘要

目的

弥漫性大 B 细胞淋巴瘤(DLBCL)是一种遗传异质性肿瘤。目前,已发现巨噬细胞封顶蛋白(CAPG)在各种癌症中作为一种调节剂发挥着关键作用。然而,其在 DLBCL 中的调控机制尚不清楚。因此,本研究旨在揭示 CAPG 在 DLBCL 中的作用机制。

方法

采用生物信息学分析预测 CAPG 在 DLBCL 中的表达及其下游靶基因。采用 qRT-PCR 检测 CAPG 和 CEBPA 的 mRNA 表达水平。采用 Western blot 检测相关蛋白的表达水平。然后,我们通过流式细胞术分析细胞周期和细胞凋亡。还采用 MTT 法检测细胞存活,采用 IHC 法检测 DLBLC 组织中 CAPG 的表达。然后,采用 ChIP 法确定 CEBPA 和 CAPG 的结合。进行体内实验,使用异种移植模型研究 CAPG 对 DLBCL 的影响。

结果

在 DLBCL 细胞和组织中发现 CAPG 表达水平较高。CAPG 可增强 DLBCL 细胞的增殖和侵袭能力,抑制细胞凋亡,并激活 PI3K/AKT 信号通路。CAPG 过表达加速了 DLBCL 细胞的恶性进展。此外,CAPG 的表达受 CEBPA 调节。

结论

CAPG 通过促进 PI3K/AKT 信号通路增强 DLBCL 细胞的增殖和侵袭,有望成为 DLBCL 的一个有前途的治疗靶点。

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