NAP1L1 interacts with hepatoma-derived growth factor to recruit c-Jun inducing breast cancer growth

Cancer Cell International

Guangyu Yao¹  Shien Cui²  Bin Gong³  Shu Liu⁴  Dajiang Song⁵  Bo Li⁶  Qian Chen⁶  Yewei Zhang⁶ 

[1] Breast Center, Department of General Surgery, Nanfang Hospital Southern Medical University, Guangzhou, China;Breast Center, Department of General Surgery, Nanfang Hospital Southern Medical University, Guangzhou, China;Breast Center, Department of General Surgery, Zhongshan City People’s Hospital, Zhongshan, Guangzhou, China;Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China;Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, 550001, Guiyang, Guizhou, People’s Republic of China;Guizhou Medical University, Guiyang, Guizhou, China;Department of Oncology Plastic Surgery, Hunan Province Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;Guizhou Medical University, Guiyang, Guizhou, China;

关键词: Breast cancer;    Oncogene;    NAP1L1;    HDGF;    C-JUN;   

DOI  :  10.1186/s12935-021-02301-3

来源: Springer

【 摘 要 】

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.

【 授权许可】

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