NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma

Cancer Manag Res. 2020 Aug 7:12:7021-7032. doi: 10.2147/CMAR.S260091. eCollection 2020.

Abstract

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 (P=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.

Keywords: cell growth and migration; intrahepatic cholangiocarcinoma; neuropilin-1; prognostic factor.