title: DDA1, a novel oncogene, promotes lung cancer progression through regulation of cell cycle.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lin
authors.identifier: 0000-0002-6031-3899
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qianmei
authors.initials: Q
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fan
authors.affiliation: Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016196:S Phase / Q000235:genetics*; D015398:Signal Transduction; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: C530105:Ccnd1 protein, mouse; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D019927:Cyclin E; C541165:DDA1 protein, human; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; C568314:cyclin E1, mouse; D019938:Cyclin D1
keywords: DDA1; cell cycle; cell proliferation; cyclins