Cheng Lin, Yang Qianmei, Li Can, Dai Lei, Yang Yang, Wang Qingnan, Ding Yu, Zhang Junfeng, Liu Lei, Zhang Shuang, Fan Ping, Hu Xun, Xiang Rong, Yu Dechao, Wei Yuquan, Deng Hongxin
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Cell Mol Med. 2017 Aug;21(8):1532-1544. doi: 10.1111/jcmm.13084. Epub 2017 Feb 17.
Lung cancer is globally widespread and associated with high morbidity and mortality. DDA1 (DET1 and DDB1 associated 1) was first discovered and registered in the GenBank database by our colleagues. DDA1, an evolutionarily conserved gene, might have significant functions. Recent reports have demonstrated that DDA1 is linked to the ubiquitin-proteasome pathway and facilitates the degradation of target proteins. However, the function of DDA1 in lung cancer was previously unknown. This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of lung cancer. We found that the expression of DDA1 in normal lung cells and tissue was significantly lower than that in lung cancer and was associated with poor prognosis. DDA1 overexpression promoted proliferation of lung tumour cells and facilitated cell cycle progression in vitro and subcutaneous xenograft tumour progression in vivo. Mechanistically, this was associated with the regulation of S phase and cyclins including cyclin D1/D3/E1. These results indicate that DDA1 promotes lung cancer progression, potentially through promoting cyclins and cell cycle progression. Therefore, DDA1 may be a potential novel target for lung cancer treatment, and a biomarker for tumour prognosis.
肺癌在全球范围内广泛存在，且发病率和死亡率都很高。DDA1（与DET1和DDB1相关的1）最初是由我们的同事在GenBank数据库中发现并登记的。DDA1是一个进化上保守的基因，可能具有重要功能。最近的报告表明，DDA1与泛素-蛋白酶体途径相关，并促进靶蛋白的降解。然而，DDA1在肺癌中的功能此前尚不清楚。本研究旨在调查DDA1是否促进肺癌的发生和进展。我们发现，DDA1在正常肺细胞和组织中的表达明显低于肺癌中的表达，且与预后不良相关。DDA1过表达促进了肺肿瘤细胞的增殖，并在体外促进了细胞周期进程，在体内促进了皮下异种移植肿瘤的进展。从机制上讲，这与S期和细胞周期蛋白（包括细胞周期蛋白D1/D3/E1）的调节有关。这些结果表明，DDA1可能通过促进细胞周期蛋白和细胞周期进程来促进肺癌进展。因此，DDA1可能是肺癌治疗的一个潜在新靶点，以及肿瘤预后的一个生物标志物。
