NAP1L1 Interacts with Hepatoma-Derived Growth Factor to Recruit C-Jun Inducing Breast Cancer Growth

Abstract

Background：Breast cancer is the top cancer in women in the world. However, its pathogenesis is still to be determined. The role and molecular mechanism of NAP1L1 in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for glioma treatment.Methods：A bioinformatics analysis was conducted to determine the differential expression of NAP1L1 in breast cancer and find the potential biomarker that interacts with NAP1L1 and HDGF. The expression of NAP1L1 in tissues was detected by using immunohistochemistry. Breast cancer cells were transfected with the corresponding lentiviral particles and siRNA. Then, MTT, Edu, plate clone formation, and subcutaneous tumorigenesis in nude mice were used to detect the cell proliferation in breast cancer. Furthermore, coimmunoprecipitation (Co-IP) assay and confocal microscopy were performed to explore the detailed molecular mechanism of NAP1L1 in breast cancer.Results：In this study, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) protein was upregulated based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Consistent with the prediction, immunohistochemistry staining showed that NAP1L1 protein expression was significantly increased in breast cancer tissues. Its elevated expression was an unfavorable factor for breast cancer clinical progression and poor prognosis. Stably or transiently knocking down NAP1L1 reduced the cell growth in vivo and in vitro via repressing the cell cycle signal in breast cancer. Furthermore, the molecular basis of NAP1L1-induced cell cycle signal was further studied. NAP1L1 interacted with the hepatoma-derived growth factor (HDGF), an oncogenic factor for tumors, and the latter subsequently recruited the key oncogenic transcription factor c-Jun, which finally induced the expression of cell cycle promoter CCND1 and thus the cell growth of breast cancer. Conclusions：Our data demonstrated that NAP1L1 functions as a potential oncogene via interacting with HDGF to recruit c-Jun in breast cancer.