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[鼻型结外NK/T细胞淋巴瘤中PRDM1表达及其与PI3K/AKT通路激活的关系]

[PRDM1 expression and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type].

作者信息

Liu J M, Liang L, Huang S S, Li T

机构信息

Department of Pathology, Peking University First Hospital, Beijing 100034, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2018 Dec 14;39(12):1010-1016. doi: 10.3760/cma.j.issn.0253-2727.2018.12.008.

Abstract

To investigate the expression of PRDM1 and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type. Immunocytochemistry and Western blot were used to detect the expression of PRDM1 and p-AKT in 10 EN-NK/T-NT tissue or 3 cell lines (PRDM1-positive YT cell line, PRDM1-negative NKL and NK92 cell lines). Nanostring gene expression profiling technique was used to detect the activation of the PI3K/AKT pathway in normal nasal mucosa, PRDM1-negative and positive EN-NK/T-NT tissue. MTS was used to detect cell proliferation, and flow cytometry was used to detect cell cycle and apoptosis. Nanostring gene expression profiling revealed that genes associated with PI3K/AKT signaling pathway (eg, IL-7, BRCA1, ITGA8, IL2RB, FASLG, CDK2, COL27A1, CSF3R, KITLG and IL-6) were highly expressed in EN-NK/T-NT cases (<0.05). Also, we found that p-AKT was highly expressed in YT cell line, but lower or not expressed in NK92 and NKL cells. In addition, LY294002, a PI3K/AKT pathway inhibitor, increased PRDM1 and PTEN expression in a dose dependent manner in YT cells. More importantly, YT cell were treated with 20 μmol/L LY294002 48 h, the proliferation rate was significantly decreasing (58.18% 100.00%, =12.770, =0.006), and the proportion of cells in G(1) phase was significantly increased (30.05% 76.93%, =11.570, <0.001). However, there was no significant difference in cell proliferation and cell cycle between NKL cells and control group (>0.05). The activation of PI3K/AKT pathway is positive associated with the expression of PRDM1 in EN-NK/T-NT, and inhibition of PI3K/AKT pathway may have significant therapeutic potential for PRDM1-positive EN-NK/T-NT.

摘要

探讨PRDM1在结外NK/T细胞淋巴瘤鼻型中的表达及其与PI3K/AKT信号通路激活的关系。采用免疫细胞化学和蛋白质印迹法检测10例结外NK/T细胞淋巴瘤鼻型组织或3种细胞系(PRDM1阳性的YT细胞系、PRDM1阴性的NKL和NK92细胞系)中PRDM1和p-AKT的表达。采用纳米串基因表达谱技术检测正常鼻黏膜、PRDM1阴性和阳性的结外NK/T细胞淋巴瘤鼻型组织中PI3K/AKT信号通路的激活情况。采用MTS法检测细胞增殖,流式细胞术检测细胞周期和凋亡。纳米串基因表达谱显示,与PI3K/AKT信号通路相关的基因(如IL-7、BRCA1、ITGA8、IL2RB、FASLG、CDK2、COL27A1、CSF3R、KITLG和IL-6)在结外NK/T细胞淋巴瘤鼻型病例中高表达(<0.05)。此外,我们发现p-AKT在YT细胞系中高表达,但在NK92和NKL细胞中低表达或不表达。此外,PI3K/AKT信号通路抑制剂LY294002在YT细胞中以剂量依赖的方式增加PRDM1和PTEN的表达。更重要的是,用20μmol/L LY294002处理YT细胞48小时后,增殖率显著降低(58.18%对100.00%,t = 12.770,P = 0.006),G(1)期细胞比例显著增加(30.05%对76.93%,t = 11.570,P < 0.001)。然而,NKL细胞与对照组之间的细胞增殖和细胞周期无显著差异(P > 0.05)。PI3K/AKT信号通路的激活与结外NK/T细胞淋巴瘤鼻型中PRDM1的表达呈正相关,抑制PI3K/AKT信号通路可能对PRDM1阳性的结外NK/T细胞淋巴瘤鼻型具有显著的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/7348219/688cf9575e13/cjh-39-12-1010-g001.jpg

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