Abstract
BackgroundBreast cancer is a common cancer among women in the world. However, its pathogenesis is still to be determined. The role and molecular mechanism of Nucleosome Assembly Protein 1 Like 1 (NAP1L1) in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for breast cancer treatment.MethodsA bioinformatics analysis was conducted to determine the differential expression of NAP1L1 in breast cancer and find the potential biomarker that interacts with NAP1L1 and hepatoma-derived growth factor (HDGF). The expression of NAP1L1 in tissues was detected by using immunohistochemistry. Breast cancer cells were transfected with the corresponding lentiviral particles and siRNA. The efficiency of transfection was measured by RT-qPCR and western blotting. 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.ResultsIn this study, 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 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 Cyclin D1(CCND1) and thus the cell growth of breast cancer.ConclusionsOur data demonstrated that NAP1L1 functions as a potential oncogene via interacting with HDGF to recruit c-Jun in breast cancer.
Highlights
Breast cancer is a serious disease in which malignant cells are formed in breast tissues
Nucleosome Assembly Protein 1 Like 1 (NAP1L1) overexpression promotes cell proliferation in breast cancer cells To explore the possible role of NAP1L1 in breast cancer, we first examined NAP1L1 expression and its correlation with clinical feature and survival prognosis in breast cancer
We explored the correlation of NAP1L1 protein expression with survival prognosis and clinical features
Summary
Breast cancer is a serious disease in which malignant cells are formed in breast tissues. NAP1L1 is more widely reported to participate in the pathogenesis of tumors It is preliminarily found as the human homolog of the yeast NAP-1 protein and promotes the cumulative nucleosome formation [8]. Elevated NAP1L1 level was shown as potential diagnostic and unfavorable prognostic biomarkers for some tumors and stimulated tumor progression and doxorubicin chemotherapy resistance in tumors including colorectal cancer [10, 11], renal cancer [12], liver cancer [13,14,15], glioblastoma [16] and pancreatic neuroendocrine neoplasm [17] These data demonstrate the significance of NAP1L1 in tumor pathogenesis. The role and molecular mechanism of Nucleosome Assembly Protein 1 Like 1 (NAP1L1) in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for breast cancer treatment
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