Department of Anus and Intestine Surgery, the First Affiliated Hospital of China Medical University, 155# North Nanjing Street, Heping District, Shenyang City, 110001, Liaoning Province, China.
Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, China.
BMC Cancer. 2023 Jun 8;23(1):526. doi: 10.1186/s12885-023-11007-w.
NEDD4 family represent an important group of E3 ligases, which regulate various cellular pathways of cell proliferation, cell junction and inflammation. Emerging evidence suggested that NEDD4 family members participate in the initiation and development of tumor. In this study, we systematically investigated the molecular alterations as well as the clinical relevance regarding NEDD4 family genes in 33 cancer types. Finally, we found that NEDD4 members showed increased expression in pancreas cancer and decreased expression in thyroid cancer. NEDD4 E3 ligase family genes had an average mutation frequency in the range of 0-32.1%, of which HECW1 and HECW2 demonstrated relatively high mutation rate. Breast cancer harbors large amount of NEDD4 copy number amplification. NEDD4 family members interacted proteins were enriched in various pathways including p53, Akt, apoptosis and autophagy, which were confirmed by further western blot and flow cytometric analysis in A549 and H1299 lung cancer cells. In addition, expression of NEDD4 family genes were associated with survival of cancer patients. Our findings provide novel insight into the effect of NEDD4 E3 ligase genes on cancer progression and treatment in the future.
NEDD4 家族是一类重要的 E3 连接酶，调节细胞增殖、细胞连接和炎症等多种细胞通路。新出现的证据表明，NEDD4 家族成员参与肿瘤的发生和发展。在这项研究中，我们系统地研究了 33 种癌症类型中 NEDD4 家族基因的分子改变及其临床相关性。最后，我们发现 NEDD4 成员在胰腺癌中表达增加，在甲状腺癌中表达降低。NEDD4 E3 连接酶家族基因的平均突变频率在 0-32.1%之间，其中 HECW1 和 HECW2 显示出相对较高的突变率。乳腺癌具有大量的 NEDD4 拷贝数扩增。NEDD4 家族成员相互作用的蛋白在包括 p53、Akt、凋亡和自噬在内的各种途径中富集，这在 A549 和 H1299 肺癌细胞中的进一步 Western blot 和流式细胞术分析中得到了证实。此外，NEDD4 家族基因的表达与癌症患者的生存有关。我们的发现为未来 NEDD4 E3 连接酶基因对癌症进展和治疗的影响提供了新的见解。
