Department of Hematology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, Fujian Province, China.
Department of Pathology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, Fujian Province, China.
Aging (Albany NY). 2020 Nov 18;12(23):23822-23835. doi: 10.18632/aging.104030.
In this study, we investigated the role of calreticulin (CALR) in the pathogenesis of natural killer/T-cell lymphoma (NKTCL). CALR expression was significantly higher in the NKTCL tissues than normal control tissues in the GSE80632 dataset. High CALR expression correlated with poorer overall survival of NKTCL patients ( = 0.0248). CALR mRNA and protein levels were significantly higher in NKTCL cell lines (NK92, SNK6, and SNT8) than normal NK cells. CALR-silenced SNK6 cells generated significantly smaller xenograft tumors in immunodeficient NCG mice than control SNK6 cells. CALR-knockdown NKTCL cells showed significantly less proliferation and Transwell migration than the controls. CALR knockdown inhibited G1-to-S phase cell cycle progression by increasing the levels of p27 cell cycle inhibitor and reducing the levels of cyclin E2 and cyclin-dependent kinase 2 (CDK2). CALR knockdown inhibited epithelial-to-mesenchymal transition (EMT) by decreasing the levels of β-catenin and TCF/ZEB1 and upregulating E-cadherin. These data demonstrate that CALR regulates the growth and progression of NKTCL cells by modulating G1-to-S cell cycle progression and EMT.
在这项研究中，我们研究了钙网织蛋白（CALR）在自然杀伤/T 细胞淋巴瘤（NKTCL）发病机制中的作用。在 GSE80632 数据集，CALR 在 NKTCL 组织中的表达明显高于正常对照组织。高 CALR 表达与 NKTCL 患者的总生存不良相关（=0.0248）。CALR 的 mRNA 和蛋白水平在 NKTCL 细胞系（NK92、SNK6 和 SNT8）中明显高于正常 NK 细胞。与对照 SNK6 细胞相比，CALR 沉默的 SNK6 细胞在免疫缺陷 NCG 小鼠中产生的异种移植肿瘤明显更小。CALR 敲低的 NKTCL 细胞的增殖和 Transwell 迁移明显低于对照。CALR 敲低通过增加 p27 细胞周期抑制剂的水平和降低细胞周期蛋白 E2 和细胞周期蛋白依赖性激酶 2（CDK2）的水平抑制 G1 期到 S 期细胞周期进程。CALR 敲低通过降低β-连环蛋白和 TCF/ZEB1 的水平和上调 E-钙黏蛋白抑制上皮间质转化（EMT）。这些数据表明，CALR 通过调节 G1 期到 S 期细胞周期进程和 EMT 来调节 NKTCL 细胞的生长和进展。
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