Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Department of General Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Oncol Rep. 2019 Nov;42(5):2130-2138. doi: 10.3892/or.2019.7322. Epub 2019 Sep 18.
It has been reported that NF‑κB activating protein (NKAP) is a transcriptional repressor of the Notch signaling pathway and is involved in the proliferation and survival of hematopoietic stem cells. In the present study, we aimed to investigate the effect of NKAP on the progression and metastasis of colon cancer. The results of immunohistochemical staining and western blot analysis showed that NKAP was upregulated in colon cancer tissues, and its expression was associated with colon cancer stages. CCK‑8, colony formation, Transwell, and flow cytometry assays were used to demonstrate that NKAP knockdown significantly suppressed the proliferation and invasion of HCT116 and HT‑29 cells, and also induced apoptosis and autophagy. By contrast, NKAP overexpression markedly promoted the proliferation and invasion of HCT‑15 cells, and inhibited cell apoptosis and autophagy. Moreover, we observed that NKAP knockdown inhibited the epithelial‑mesenchymal transition (EMT) process in HCT116 and HT‑29 cells, while NKAP overexpression promoted EMT in HCT‑15 cells. Furthermore, NKAP knockdown inhibited activation of the Akt/mTOR signaling pathway by downregulating the phosphorylation of Akt and mTOR, as well as their downstream proteins, whereas NKAP overexpression promoted the Akt/mTOR signaling pathway. Additionally, expression of P65 was downregulated by silencing of NKAP and upregulated by NKAP overexpression. These data suggest that NKAP functions as an oncogene in the growth and invasion of colon cancer in vitro.
据报道，NF-κB 激活蛋白（NKAP）是 Notch 信号通路的转录抑制剂，参与造血干细胞的增殖和存活。在本研究中，我们旨在研究 NKAP 对结肠癌进展和转移的影响。免疫组织化学染色和 Western blot 分析的结果表明，NKAP 在结肠癌组织中上调，其表达与结肠癌分期相关。CCK-8、集落形成、Transwell 和流式细胞术实验表明，NKAP 敲低显著抑制了 HCT116 和 HT-29 细胞的增殖和侵袭，并且诱导了细胞凋亡和自噬。相比之下，NKAP 过表达显著促进了 HCT-15 细胞的增殖和侵袭，并且抑制了细胞凋亡和自噬。此外，我们观察到 NKAP 敲低抑制了 HCT116 和 HT-29 细胞中的上皮间质转化（EMT）过程，而 NKAP 过表达促进了 HCT-15 细胞中的 EMT。此外，NKAP 敲低通过下调 Akt 和 mTOR 的磷酸化及其下游蛋白来抑制 Akt/mTOR 信号通路的激活，而 NKAP 过表达则促进 Akt/mTOR 信号通路。此外，沉默 NKAP 会下调 P65 的表达，而过表达 NKAP 则会上调 P65 的表达。这些数据表明，NKAP 在体外作为结肠癌生长和侵袭的癌基因发挥作用。
