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

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

[Article in Chinese]
J M Liu  1 , L Liang, S S Huang, T Li
Affiliations

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

[Article in Chinese]
J M Liu et al. Zhonghua Xue Ye Xue Za Zhi. .

Abstract
in English, Chinese

Objective: To investigate the expression of PRDM1 and its relationship with PI3K/AKT pathway activation in extranodal NK/T cell lymphoma-nasal type. Methods: 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. Results: 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 (P<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% vs 100.00%, t=12.770, P=0.006), and the proportion of cells in G(1) phase was significantly increased (30.05% vs 76.93%, t=11.570, P<0.001). However, there was no significant difference in cell proliferation and cell cycle between NKL cells and control group (P>0.05). Conclusion: 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.

目的： 探讨抑癌基因PRDM1在结外NK/T细胞淋巴瘤-鼻型（EN-NK/T-NT）中的表达及其与PI3K/AKT通路活化的关系。 方法： 以10例EN-NK/T-NT患者病理组织标本和PRDM1阳性细胞系YT细胞、PRDM1缺失细胞系NKL、NK92细胞为研究对象，采用免疫细胞化学和Western blot法检测PRDM1、p-AKT的表达，采用NanoString基因表达谱技术检测PI3K/AKT通路在正常鼻黏膜、PRDM1阴性和阳性EN-NK/T-NT组织中的激活情况，采用MTS法检测YT、NKL和NK92细胞增殖活性，采用流式细胞术检测细胞周期和细胞凋亡。 结果： ①NanoString基因表达谱分析结果显示PRDM1阳性组PI3K/AKT信号通路IL-7、BRCA1、ITGA8、IL2RB、FASLG、CDK2、COL27A1、CSF3R、KITLG、IL-6的表达明显高于对照组，差异均有统计学意义（P值均<0.05）。②免疫细胞化学和Western blot法检测结果显示p-AKT在YT细胞系中高表达，而在NK92和NKL细胞中低表达或不表达。③Western blot法检测结果显示，PI3K/AKT通路抑制剂LY294002作用24 h后YT细胞PRDM1和PTEN的表达水平升高，且呈剂量依赖性。④LY294002（20 μmol/L）作用48 h后，与对照组比较，YT细胞增殖率较对照组明显降低（100.00%对58.18%，t=－12.770，P=0.006），G(1)期细胞比例明显增高（30.05%对76.93%，t=11.570，P<0.001），差异均有统计学意义；但NKL细胞与对照组比较细胞增殖和细胞周期的差异均无统计学意义（P值均>0.05）。 结论： EN-NK/T-NT中PI3K/AKT通路活化与PRDM1阳性表达相关，抑制PI3K/AKT通路有望成为PRDM1阳性EN-NK/T-NT的治疗手段。.

Keywords: Genes, PRDM1; Lymphoma, extra-nodal NK-T-cell; Phosphatidylinositol 3-kinase; Protein kinases.

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Figures

图1
图1. 不同患者组PI3K/AKT信号通路平均得分散点图
图2
图2. 免疫细胞化学法检测p-AKT在NK/T细胞淋巴瘤细胞系YT（A）、NK92（B）和NKL（C）细胞中的表达（高倍）
图3
图3. Western blot法检测PRDM1和p-AKT蛋白在YT、NK92、NKL细胞中的表达
1：YT细胞；2：NK92细胞；3：NKL细胞
图4
图4. Western blot法检测LY294002处理YT细胞24 h后PRDM1和PTEN蛋白的表达
1：对照组；2：10 µmol/L LY294002；3：20 µmol/L LY294002
图5
图5. 流式细胞术检测LY294002对YT、NK92和NKL细胞周期的影响（*P<0.05）
See this image and copyright information in PMC

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