FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma
Authors Sun H, Liu K, Huang J, Sun Q, Shao C, Luo J, Xu L, Shen Y, Ren B
Received 15 October 2018
Accepted for publication 14 March 2019
Published 17 April 2019 Volume 2019:12 Pages 2829—2842
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr Federico Perche
Haijun Sun,1–3,* Kaichao Liu,4,* Jianfeng Huang,1,2,* Qi Sun,5 Chenye Shao,4 Jing Luo,4 Lin Xu,1,2 Yi Shen,4 Binhui Ren1,2
1Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, People’s Republic of China; 2Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, the First People’s Hospital of Lianyungang City, Nanjing Medical University Affiliated Lianyungang Clinical College, Lianyungang, Jiangsu, People’s Republic of China; 4Department of Cardiothoracic Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 5Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, Germany
*These authors contributed equally to this work
Purpose: Lung adenocarcinoma (LUAD) is a main subtype of lung cancer, which is the leading cause of cancer-related deaths. The five-year survival rates of lung cancer patients are still comparatively low. Therefore, potential therapeutic targets are urgently needed to improve the survival of lung cancer patients. In this study, we identified FAM111B as an oncogene and potential therapeutic target for LUAD.
Methods: The TCGA database and tissue microarray analysis were used to compare the expression of FAM111B in tumor tissue and normal tissues and evaluate the relationship between FAM111B expression and clinical survival. FAM111B was knocked down and overexpressed to observe whether FAM111B could affect the proliferation, migration, cell cycle, and apoptosis of LUAD cells in vivo and in vitro.
Results: FAM111B was highly expressed in tumor tissues compared with normal tissues (P<0.01). LUAD patients with hyper-expression of FAM111B had a lower recurrence-free survival (P<0.01) and shorter overall survival (P<0.01). Knocking down FAM111B inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Silencing FAM111B could arrest LUAD cells at G2/M phase and increase apoptosis. Overexpression of FAM111B promoted the growth of lung cancer cells. FAM111B was identified as a direct target of p53 in existing researches by chip-seq analysis. Bioinformatics analysis predicted that FAM111B could directly bind to BAG3 (BCL2 associated athanogene 3). When FAM111B was down-regulated, both expression of BAG 3 and BCL2 were significantly reduced, whereas decreasing the expression of BAG3 had no effect on FAM111B.
Conclusions: Our study indicated that FAM111B might be an oncogene and potential therapeutic target in LUAD which could be involved in the regulation of tumor cells by p53 signaling pathway and play an important role in the process of cell cycle and apoptosis by influencing the expression of BAG3 and BCL2.
Keywords: apoptosis, p53, BAG3, FAM111B, lung adenocarcinoma, oncogene
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