NRBP2 Overexpression Inhibits Cell Proliferation and Migration and Increases Cisplatin Sensitivity in Intrahepatic Cholangiocarcinoma

AIMS: Nuclear receptor binding protein 2 is ubiquitously expressed in all tissues in humans. However, few studies have reported the function of nuclear receptor binding protein 2 in human cancers. METHODS: Immunohistochemistry and Reverse Transcription-PCR (RT-PCR) were used to detect nuclear receptor binding protein 2 expression in intrahepatic cholangiocarcinoma tissues. Cell Counting Kit-8 assay, flow cytometry, Transwell assay, wound healing assay, and Western blotting were used for the functional study of nuclear receptor binding protein 2. All statistical analyses were performed using SPSS 19.0. RESULTS: Survival analysis showed that high expression of nuclear receptor binding protein 2 led to better prognosis. Overexpressed nuclear receptor binding protein 2 can inhibit the proliferation rate of cholangiocarcinoma cells while having a slight effect on cell apoptosis. Gain-of-function experiments showed that overexpressed nuclear receptor binding protein 2 could lead to G1 phase arrest in RBE and CCLP cell lines. Furthermore, Transwell assay showed that overexpressed nuclear receptor binding protein 2 could inhibit the migration ability of RBE and CCLP cell lines. Western blot analysis showed that E-cadherin was upregulated, while N-cadherin and vimentin were downregulated. In addition, we observed that overexpressed nuclear receptor binding protein 2 can also increase the cisplatin sensitivity of cholangiocarcinoma cells by regulating the Mammalian Target of Rapamycin (mTOR) pathway. CONCLUSIONS: Our study observed that nuclear receptor binding protein 2 played a tumor suppressive role in intrahepatic cholangiocarcinoma, which may be attributable to the induction of G1 phase arrest and inhibition of progression of epithelial–mesenchymal transition, and overexpression of nuclear receptor binding protein 2 leads to improved efficiency of cisplatin treatment.