神经纤毛蛋白1（NRP1）是肝内胆管癌的一个预后因素，并促进其细胞生长和迁移。
NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma.
作者信息
Wu Yong-Na, He Li-Hong, Bai Zhong-Tian, Li Xun
机构信息
Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, People's Republic of China.
Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou 730000, Gansu Province, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Aug 7;12:7021-7032. doi: 10.2147/CMAR.S260091. eCollection 2020.
BACKGROUND
Neuropilin-1 (NRP-1) participates in cancer cell proliferation and metastasis as a multifunctional co-receptor by interacting with multiple signaling pathways. However, few studies have addressed the precise function and prognosis analysis of NRP1 in intrahepatic cholangiocarcinoma (ICC). We aimed to study the correlations between NRP1 and clinicopathological characteristics and NRP1 effect on ICC cell line functions.
METHODS
NRP1 mRNA and its protein levels in human ICC tissues and cell lines were detected by IHC, qRT-PCR, and WB method. Transwell, wound healing, and CCK-8 assays were performed to verify the effects of NRP1 knockdown and overexpression on cell migration and proliferation capability.
RESULTS
NRP1 proteins and mRNA levels increased in ICC tissues compared to those in paired adjacent non-tumor tissues. High NRP1 expression of ICC tissues was related to poor prognosis. NRP1 expression level was expected to be an independent prognosticator for overall survival and cumulative tumor recurrence, and was closely related to tumor number (=0.047). Knockdown of NRP1 inhibited cell proliferation and migration capability of RBE cells in vitro, and NRP1 overexpression in 9810 cells accelerated proliferation and migration. Additionally, NRP1 may promote cell proliferation and migration in ICC via the FAK/PI3-K/AKT pathway.
CONCLUSION
As an oncogene, NRP1 may function as a candidate target and prognostic biomarker of value for ICC therapy.
背景
神经纤毛蛋白-1（NRP-1）作为一种多功能共受体，通过与多种信号通路相互作用参与癌细胞的增殖和转移。然而，关于NRP1在肝内胆管癌（ICC）中的精确功能和预后分析的研究较少。我们旨在研究NRP1与临床病理特征之间的相关性以及NRP1对ICC细胞系功能的影响。
方法
采用免疫组化（IHC）、实时定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（WB）检测人ICC组织和细胞系中NRP1 mRNA及其蛋白水平。进行Transwell实验、伤口愈合实验和CCK-8实验，以验证NRP1基因敲低和过表达对细胞迁移和增殖能力的影响。
结果
与配对的相邻非肿瘤组织相比，ICC组织中NRP1蛋白和mRNA水平升高。ICC组织中NRP1的高表达与预后不良相关。NRP1表达水平有望成为总生存期和累积肿瘤复发的独立预后指标，且与肿瘤数量密切相关（P = 0.047）。敲低NRP1可抑制体外RBE细胞的增殖和迁移能力，而在9810细胞中过表达NRP1则加速增殖和迁移。此外，NRP1可能通过FAK/PI3-K/AKT途径促进ICC细胞的增殖和迁移。
结论
作为一种癌基因，NRP1可能作为ICC治疗中有价值的候选靶点和预后生物标志物发挥作用。
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