Colorectal Disease of Guangdong Provincial Hospital of Chinese Medicine, the 2nd Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Sep 25;54(9):1234-1243. doi: 10.3724/abbs.2022124.
Colon cancer is a common malignant tumor. However, its pathogenesis still needs further study. In this study, we explored the role of nucleosome assembly protein 1-like 1 (NAP1L1) in colon cancer and its underlying mechanism. Based on analysis of The Cancer Genome Atlas data, we found that NAP1L1 is augmented in colorectal cancer, and the elevated NAP1L1 expression is associated with a poor prognosis in patients with colon cancer. Immunohistochemistry staining results showed that upregulated NAP1L1 protein level is an unfavorable factor that stimulates colon cancer progression. To further investigate the role of NAP1L1 in colon cancer, we established a colon cancer cell line with knockdown, and found that repressing NAP1L1 expression in colon cancer cells markedly reduces cell proliferation and o by MTT assay, colony formation, EdU incorporation, and subcutaneous tumorigenesis in nude mice. Furthermore, we found that NAP1L1 binds to HDGF, recruits DDX5, and induces β-catenin/CCND1 signaling, which promotes colon cancer cell proliferation. Finally, transfection with or restores cell growth in -knockdown colon cancer cells by upregulating DDX5/β-catenin/CCND1 signaling. Our study demonstrates that NAP1L1 functions as a potential oncogene that promotes colon cancer tumorigenesis by binding to HDGF, which stimulates DDX5/β-catenin/CCND1 signaling.
结直肠癌是一种常见的恶性肿瘤。然而，其发病机制仍需要进一步研究。在本研究中，我们探讨了核小体组装蛋白 1 样 1（NAP1L1）在结直肠癌中的作用及其潜在机制。基于对癌症基因组图谱数据的分析，我们发现 NAP1L1 在结直肠癌中扩增，升高的 NAP1L1 表达与结直肠癌患者的预后不良相关。免疫组织化学染色结果表明，NAP1L1 蛋白水平上调是促进结肠癌进展的不利因素。为了进一步研究 NAP1L1 在结直肠癌中的作用，我们建立了敲低 NAP1L1 的结直肠癌细胞系，发现抑制结直肠癌细胞中 NAP1L1 的表达通过 MTT assay、集落形成、EdU 掺入和裸鼠皮下肿瘤形成显著降低细胞增殖和肿瘤生长。此外，我们发现 NAP1L1 与 HDGF 结合，募集 DDX5，并诱导 β-连环蛋白/CCND1 信号通路，促进结肠癌细胞增殖。最后，转染 或通过上调 DDX5/β-连环蛋白/CCND1 信号通路恢复 - 敲低结肠癌细胞的生长。我们的研究表明，NAP1L1 通过与 HDGF 结合作为一种潜在的致癌基因发挥作用，通过刺激 DDX5/β-连环蛋白/CCND1 信号通路促进结直肠癌肿瘤发生。
