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DDA1 a novel oncogene promotes lung cancer progression through regulation of cell cycle

机译:DDA1是一种新型致癌基因可通过调节细胞周期促进肺癌的进展

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摘要

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.
机译:肺癌在全球范围内广泛存在,并与高发病率和高死亡率有关。 DDA1(与DET1和DDB1相关联的1)最早是由我们的同事发现并注册到GenBank数据库中的。 DDA1是一种进化保守基因,可能具有重要功能。最近的报道表明,DDA1与泛素-蛋白酶体途径有关,并促进靶蛋白的降解。但是,DDA1在肺癌中的功能以前未知。这项研究旨在调查DDA1是否有助于肺癌的发生和发展。我们发现正常肺细胞和组织中DDA1的表达明显低于肺癌,并且与不良预后有关。 DDA1的过表达促进了肺肿瘤细胞的增殖,并促进了体外的细胞周期进程和体内的皮下异种移植肿瘤进程。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发展而促进肺癌的发展。因此,DDA1可能是肺癌治疗的潜在新靶标,也是肿瘤预后的生物标志物。

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