Kai Wang1,2, Xiao Qu1, Shaorui Liu1, Xudong Yang1, Fenglong Bie1, Yu Wang1, Cuicui Huang1, Jiajun Du3,4. 1. Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. 2. Department of Healthcare Respiratory, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. 3. Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. dujiajun@sdu.edu.cn. 4. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. dujiajun@sdu.edu.cn.
Abstract
PURPOSE: F-box proteins, as components of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase, can specifically bind to substrates and regulate multiple tumor behaviors. However, the role of F-box proteins in squamous-cell lung carcinoma (SqCLC) has not been established. METHODS: We identified the differentially expressed F-box protein-encoding genes in SqCLC by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognosis data were evaluated using the Kaplan-Meier (KM) plotter website. The FBXO5 and FBXO45 mRNA levels were analyzed by real time RT-PCR. The impact of the inhibition of these genes with si-RNA on apoptosis and migration was also investigated. RESULTS: The FBXO45 and FBXO5 genes were significantly up-regulated in SqCLC compared with normal lung (p values = 0.002 and 0.025, respectively). FBXO45 was significantly elevated in each tumorigenic step, including dysplasia, in situ and SqCLC. The RT-PCR analysis results showed that FBXO5 and FBXO45 were elevated in cancer tissues (p values = 0.024 and 0.004, respectively). Overexpression of FBXO5 and FBXO45 was associated with shorter overall survival (OS) in the SqCLC patients from the K-M plotter database [FBXO5 HR: 1.53 (1.03-2.28), p = 0.036]; [FBXO45 HR: 1.47 (1.03-2.08), p = 0.030]. The GO and KEGG pathway analysis showed that FBXO5 and FBXO45 were associated with cell cycle and adhesion, respectively. Knockdown of FBXO5 leads to increased apoptosis, while knockdown of FBXO45 facilitates the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: Our results provide evidence that FBXO45 and FBXO5 may play a key role in tumorigenesis and prognosis of SqCLC.
PURPOSE: F-box proteins, as components of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase, can specifically bind to substrates and regulate multiple tumor behaviors. However, the role of F-box proteins in squamous-cell lung carcinoma (SqCLC) has not been established. METHODS: We identified the differentially expressed F-box protein-encoding genes in SqCLC by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognosis data were evaluated using the Kaplan-Meier (KM) plotter website. The FBXO5 and FBXO45 mRNA levels were analyzed by real time RT-PCR. The impact of the inhibition of these genes with si-RNA on apoptosis and migration was also investigated. RESULTS: The FBXO45 and FBXO5 genes were significantly up-regulated in SqCLC compared with normal lung (p values = 0.002 and 0.025, respectively). FBXO45 was significantly elevated in each tumorigenic step, including dysplasia, in situ and SqCLC. The RT-PCR analysis results showed that FBXO5 and FBXO45 were elevated in cancer tissues (p values = 0.024 and 0.004, respectively). Overexpression of FBXO5 and FBXO45 was associated with shorter overall survival (OS) in the SqCLC patients from the K-M plotter database [FBXO5 HR: 1.53 (1.03-2.28), p = 0.036]; [FBXO45 HR: 1.47 (1.03-2.08), p = 0.030]. The GO and KEGG pathway analysis showed that FBXO5 and FBXO45 were associated with cell cycle and adhesion, respectively. Knockdown of FBXO5 leads to increased apoptosis, while knockdown of FBXO45 facilitates the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: Our results provide evidence that FBXO45 and FBXO5 may play a key role in tumorigenesis and prognosis of SqCLC.
Entities:
Keywords:
Apoptosis; Bioinformatics; F-Box proteins; Prognosis; Squamous cell lung cancer
Authors: David S Ettinger; Douglas E Wood; Dara L Aisner; Wallace Akerley; Jessica Bauman; Lucian R Chirieac; Thomas A D'Amico; Malcolm M DeCamp; Thomas J Dilling; Michael Dobelbower; Robert C Doebele; Ramaswamy Govindan; Matthew A Gubens; Mark Hennon; Leora Horn; Ritsuko Komaki; Rudy P Lackner; Michael Lanuti; Ticiana A Leal; Leah J Leisch; Rogerio Lilenbaum; Jules Lin; Billy W Loo; Renato Martins; Gregory A Otterson; Karen Reckamp; Gregory J Riely; Steven E Schild; Theresa A Shapiro; James Stevenson; Scott J Swanson; Kurt Tauer; Stephen C Yang; Kristina Gregory; Miranda Hughes Journal: J Natl Compr Canc Netw Date: 2017-04 Impact factor: 11.908
Authors: Mathias Uhlen; Cheng Zhang; Sunjae Lee; Evelina Sjöstedt; Linn Fagerberg; Gholamreza Bidkhori; Rui Benfeitas; Muhammad Arif; Zhengtao Liu; Fredrik Edfors; Kemal Sanli; Kalle von Feilitzen; Per Oksvold; Emma Lundberg; Sophia Hober; Peter Nilsson; Johanna Mattsson; Jochen M Schwenk; Hans Brunnström; Bengt Glimelius; Tobias Sjöblom; Per-Henrik Edqvist; Dijana Djureinovic; Patrick Micke; Cecilia Lindskog; Adil Mardinoglu; Fredrik Ponten Journal: Science Date: 2017-08-18 Impact factor: 47.728
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
Authors: Corey J Langer; Coleman Obasaju; Paul Bunn; Philip Bonomi; David Gandara; Fred R Hirsch; Edward S Kim; Ronald B Natale; Silvia Novello; Luis Paz-Ares; Maurice Pérol; Martin Reck; Suresh S Ramalingam; Craig H Reynolds; Mark A Socinski; David R Spigel; Heather Wakelee; Carlos Mayo; Nick Thatcher Journal: J Thorac Oncol Date: 2016-08-26 Impact factor: 15.609