NKAP functions as an oncogene and its expression is induced by CoCl2 treatment in breast cancer via AKT/mTOR signaling pathway

• Main Authors: Liu J, Wang H, Yin Y, Li Q, Zhang M
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-10-01
• Series: Cancer Management and Research
• Subjects: NKAP; breast cancer; hypoxia; AKT/mTOR signaling pathway
• Online Access: https://www.dovepress.com/nkap-functions-as-an-oncogene-and-its-expression-is-induced-by-cocl2-t-peer-reviewed-article-CMAR

Jiangtao Liu,1 Honghui Wang,2 Yanhai Yin,1 Qing Li,3 Mei Zhang3 1Department of Internal Medical Oncology, Binzhou Central Hospital, Binzhou 251700, Shandong, People’s Republic China; 2Department of Breast and Thyroid Surgery, Binzhou Central Hospital, Binzhou 251700, Shandong, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250000, Shandong, People’s Republic of China Purpose: NKAP plays an important role in transcriptional repression, T-cell development, maturation and function acquisition, maintenance and survival of hematopoietic stem cells, and RNA splicing. In this study, we tried to explore the physiological role of NKAP in breast cancer.Methods: We investigated NKAP expression in breast cancer patients and normal controls and its correlation with survival in breast cancer patients by searching on GEPIA. We knocked down the expression of NKAP in MCF-7 cells by RNAi technique and studied its effect on cell proliferation, migration, invasion, and apoptosis. And we revealed the effect of NKAP on MCF-7 cells under hypoxic conditions in vitro.Results: NKAP was differentially expressed in breast cancer and normal tissues and is a potential prognostic indicator of breast cancer. Subsequently, NKAP knockdown significantly inhibited the proliferation and clonality of MCF-7 cells and induced its apoptosis through caspase 3-dependent pathway. In addition, knockdown of NKAP could strongly inhibit the migration and invasion of MCF-7 cells. In MCF-7 cells, NKAP affected the AKT/mTOR signaling pathway and markedly reduced the phosphorylation of AKT and mTOR, as well as the downstream protein. What’s interesting is CoCl2 was found to induce NKAP expression in MCF-7 cells. Downregulation of NKAP hindered the impact of CoCl2 on the MCF-7 cells, including cell proliferation and invasion, by adjusting AKT/mTOR signaling.Conclusion: NKAP functioned as an oncogene, and its expression was induced by hypoxia in breast cancer via AKT/mTOR signaling pathway. Keywords: NKAP, breast cancer, hypoxia, AKT/mTOR signaling pathway