ANP32E 的过表达与胰腺癌的预后不良相关，并通过调节 β-连环蛋白促进细胞增殖和迁移。
Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin.
机构信息
Pancreatic and Gastric Surgery Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
出版信息
BMC Cancer. 2020 Nov 4;20(1):1065. doi: 10.1186/s12885-020-07556-z.
BACKGROUND
Pancreatic cancer is a malignant tumor with high mortality. Acidic nuclear phosphoprotein 32 family member E (ANP32E), a specific H2A.Z chaperone, has been shown to contribute to breast cancer development. However, the significance of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the role of ANP32E in pancreatic cancer.
METHODS
The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and the correlation between ANP32E expression and patients' survival were analyzed from the TCGA database. ANP32E was over-expressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle and transwell experiments were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression.
RESULTS
ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor prognosis in pancreatic cancer patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E over-expression promoted the proliferation and migration of both cells. In addition, ANP32E accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells.
CONCLUSION
Our results propose that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.
背景
胰腺癌是一种死亡率很高的恶性肿瘤。酸性核磷蛋白 32 家族成员 E（ANP32E）是一种特定的 H2A.Z 伴侣，已被证明有助于乳腺癌的发展。然而，ANP32E 在胰腺癌中的意义尚不清楚。本研究旨在探讨 ANP32E 在胰腺癌中的作用。
方法
从 TCGA 数据库中分析 179 例胰腺癌组织和 171 例正常组织中 ANP32E 的表达情况，以及 ANP32E 表达与患者生存的相关性。利用慢病毒过表达和沉默 ANP32E。利用 siRNA 敲低 β-catenin。通过 CCK8、集落形成、细胞周期和 Transwell 实验测定细胞增殖和迁移。通过 qRT-PCR 和 Western blot 检测 mRNA 和蛋白表达。
结果
ANP32E 在胰腺癌组织和细胞中上调。ANP32E 的上调预示着胰腺癌患者预后不良。慢病毒介导的 ANP32E 敲低抑制了 PANC1 和 MIA 细胞的增殖、集落生长和迁移。相比之下，ANP32E 的过表达促进了这两种细胞的增殖和迁移。此外，ANP32E 加速了 PANC1 和 MIA 细胞的细胞周期进程。分子实验表明，ANP32E 激活了 β-catenin/细胞周期蛋白 D1 信号通路。β-catenin 沉默减少了 ANP32E 过表达细胞的增殖和迁移。
结论
我们的结果表明，ANP32E 通过激活 β-catenin 发挥致癌基因的作用，在胰腺癌中发挥作用。
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