PHD-finger domain protein 5A functions as a novel oncoprotein in lung adenocarcinoma.
BACKGROUND
PHD-finger domain protein 5A (PHF5A) is a highly conserved small transcriptional regulator also involved in pre-mRNA splicing; however, its biological functions and molecular mechanisms in non-small cell lung cancer (NSCLC) have not yet been investigated. The purpose of this study was to determine the functional relevance and therapeutic potential of PHF5A in lung adenocarcinoma (LAC).


METHODS
The expression of PHF5A in LAC tissues and adjacent non-tumor (ANT) tissues was investigated using immunohistochemistry of a tissue microarray, qRT-PCR, western blot and bioinformatics. The function of PHF5A was determined using several in vitro assays and also in vivo assay by lentiviral vector-mediated PHF5A depletion in LAC cell lines.


RESULTS
PHF5A was highly upregulated in LAC tissues compared with the ANT counterparts, and closely associated with tumor progression and poor patient prognosis. These results were further confirmed by findings of the TCGA database. Moreover, functional studies demonstrated that PHF5A knockdown not only resulted in reduced cell proliferation, increased cell apoptosis, and cell cycle arrest, but also suppressed migration and invasion in LAC cells. PHF5A silencing was also found to inhibit LAC tumor growth in nude mice. Microarray and bioinformatics analyses revealed that PHF5A depletion led to dysregulation of multiple tumor signaling pathways; selected factors in key signaling pathways were verified in vitro.


CONCLUSIONS
The data suggest for the first time that PHF5A is an oncoprotein that contributes to LAC progression by regulating multiple signaling pathways, and may constitute a prognostic factor and potential new therapeutic target in NSCLC.
['Yang|Yan|Y|', 'Zhu|Jian|J|', 'Zhang|Tiantian|T|', 'Liu|Jing|J|', 'Li|Yumei|Y|', 'Zhu|Yue|Y|', 'Xu|Lingjie|L|', 'Wang|Rui|R|', 'Su|Fang|F|', 'Ou|Yurong|Y|', 'Wu|Qiong|Q|']
D000077192:Adenocarcinoma of Lung D000328:Adult D000368:Aged D000818:Animals D017209:Apoptosis D014408:Biomarkers, Tumor D002352:Carrier Proteins D045744:Cell Line, Tumor D049109:Cell Proliferation D002471:Cell Transformation, Neoplastic D019295:Computational Biology D004195:Disease Models, Animal D018450:Disease Progression D005260:Female D015870:Gene Expression D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D053263:Gene Regulatory Networks D064593:Heterografts D006801:Humans D008297:Male D051379:Mice D008875:Middle Aged D060787:Neoplasm Grading D009362:Neoplasm Metastasis D009367:Neoplasm Staging D015513:Oncogene Proteins D016601:RNA-Binding Proteins D046888:Tissue Array Analysis D015534:Trans-Activators
Lung adenocarcinoma PHF5A Proliferation Prognostic biomarker Tumor invasion