Identification of aberrantly expressed F-box proteins in squamous-cell lung carcinoma
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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.
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.
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).
Our results provide evidence that FBXO45 and FBXO5 may play a key role in tumorigenesis and prognosis of SqCLC.
KeywordsSquamous cell lung cancer F-Box proteins Prognosis Apoptosis Bioinformatics
This study was funded by National Natural Science Foundation of China (8160101782), and Key Research and Development Plan of Shandong Province (2015GSF118063).
Compliance with ethical standards
Conflict of interest
Jiajun Du declares that he has no conflict of interest. Kai Wang declares that he has no conflict of interest. Xiao Qu declares that he has no conflict of interest. Shaorui Liu declares that he has no conflict of interest. Xudong Yang declares that he has no conflict of interest. Fenglong Bie declares that he has no conflict of interest. Yu Wang declares that she has no conflict of interest. Cuicui Huang declares that she has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethic community of Shandong Provincial Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants.