NKAP functions as an oncogene in Ewing sarcoma cells partly through the AKT signaling pathway

作者：Feng Li, Jingtao Wu, Pengfei Wang, Li‐Zhen Qu · 发表于：Experimental and Therapeutic Medicine · 年份：2019 · DOI：10.3892/etm.2019.7925 · 被引用次数：6 · 研究领域：Immune Cell Function and Interaction、Sarcoma Diagnosis and Treatment、RNA Interference and Gene Delivery

NF-κB activating protein (NKAP) is a highly conserved protein involved in transcriptional repression, immune cell development, maturation, acquisition of functional competency and maintenance of hematopoiesis. In the present study, the function of NKAP in the progress of Ewing sarcoma (ES) was investigated. It was identified that NKAP is highly expressed in ES cells when compared with human mesenchymal stem cells (MSCs). NKAP was knocked-down in human ES cell lines A673 and RD-ES using small interfering (si)RNA transfection. The effectiveness of transfection was then verified using reverse transcription-quantitative PCR and western blot analysis to determine mRNA and protein levels, respectively. The results of the proliferation assays indicated that the knockdown of NKAP inhibited the proliferation and clonogenic abilities of human ES cells. Transwell assays further indicated that cell invasion and migration were significantly inhibited by NKAP knockdown, which may be mediated by downregulation of matrix metalloproteinase (MMP)-9 activity. Gain-of-function analysis also demonstrated the positive role NKAP played in the proliferation, invasion and migration of ES cells. Cell apoptosis was evaluated by flow cytometry, which identified that apoptotic cells were significantly increased when NKAP was silenced. In addition, downregulation of NKAP increased the levels of Bax and cleaved caspase 3, but decreased Bcl2 levels, which suggested that the mitochondrial apoptosis pathway w...