Expression patterns of Phf5a/PHF5A and Gja1/GJA1 in rat and human endometrial cancer

Falck, Eva; Klinga-Levan, Karin

doi:10.1186/1475-2867-13-43

Cited by 19 publications

(16 citation statements)

References 26 publications

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“…Assessment of PHF5A function enrichment was performed with IPA bioinformatics tools; the two classifications of “Cancer” and “Cell cycle” were significant. This was consistent with previous findings [ 13 , 14 ] and the above experimental data, indicating that PHF5A regulates the cell cycle to participate in tumor development. IGFBP3, PIK3CB, AKT, DDIT3, Skp2, and P53 were subsequently retrieved by the pathway enrichment analysis.…”

Section: Discussionsupporting

confidence: 94%

“…These results were further evidenced by TCGA data. Consistent with these findings, Falck et al [ 14 ] found that Phf5a gene expression was significantly increased in endometrial cancer compared with the human benign endometrial tissue, suggesting that expression changes of this gene may be involved in endometrial cancer development. Therefore, we consider that PHF5A may be a potentially highly aggressive and unfavorable prognostic biomarker in LAC.…”

Section: Discussionmentioning

confidence: 66%

“…Assessing the association of PHF5A with tumors, Falck et al [ 14 ] found that PHF5A expression in endometrial adenocarcinoma was increased compared with that of benign samples. In addition, Hubert et al [ 13 ] demonstrated a novel requirement for PHF5A in glioblastoma stem cell initiation and maintenance, by showing that PHF5A knockdown disrupted splicing of multiple essential genes and induced cell cycle arrest and loss of viability.…”

Section: Introductionmentioning

confidence: 99%

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PHD-finger domain protein 5A functions as a novel oncoprotein in lung adenocarcinoma

Yang

Zhu

Zhang

et al. 2018

J Exp Clin Cancer Res

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BackgroundPHD-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).MethodsThe 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.ResultsPHF5A 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0736-0) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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PHD-finger domain protein 5A functions as a novel oncoprotein in lung adenocarcinoma

Yang

Zhu

Zhang

et al. 2018

J Exp Clin Cancer Res

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“…Recent studies in human malignancies, implicated Phf5a in endometrial cancer and glioblastoma 23, 42 . Although Phf5a is suggested to interact with ATP-dependent helicases and the U2 snRNP spliceosome 23, 43 , its silencing surprisingly only affects exon recognition and splicing in glioblastoma stem cells (GSCs) but not their normal counterpart neural stem cells (NSCs) 23 .…”

Section: Discussionmentioning

confidence: 99%

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a

et al. 2016

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Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf5a) in ESC self-renewal and ascribe its role in regulating pluripotency, cellular reprogramming, and myoblast specification. We demonstrate that Phf5a is essential for maintaining pluripotency, since depleted ESCs exhibit hallmarks of differentiation. Mechanistically, we attribute Phf5a function to the stabilization of the Paf1 transcriptional complex and control of RNA polymerase II elongation on pluripotency loci. Apart from an ESC-specific factor, we demonstrate that Phf5a controls differentiation of adult myoblasts. Our findings suggest a potent mode of regulation by the Phf5a in stem cells, which directs their transcriptional program ultimately regulating maintenance of pluripotency and cellular reprogramming.

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“…Gja1 is a connexin shown to be down-regulated in cancer cells and, moreover, connexins have previously been shown to act as tumor suppressors [25,26]. Falck and Karin-Levan (2013) previously found Phf5a/ PHF5Ato be aberrantly expressed in estrogen dependent endometrial adenocarcinoma (EAC) tumors from rat and human type I tumors [27]. Additionally, homologs of Phf5a in Saccharomyces cerevisiae and Schizosaccharomyces pombe have been identified as critical genes in pre-mRNA splicing and cell cycle regulation in these species, as cells lacking this gene showed an arrest in the spliceosome assembly and failed to go through the cell cycle, respectively [11,28].…”

Section: Spliceosome Component Coding Genes Have Previously Been Shownmentioning

confidence: 99%

A Systems Biology View of the Spliceosome Component Phf5a in Relation to Estrogen and Cancer

Vallabhu¹

2014

J Comput Sci Syst Biol

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Cancer is a broad term for a wide spectrum of diseases and which involves the alteration in expression levels of several hundreds of genes. As such, the study of the disease from a systems biology point of view becomes rational, as the properties of a system as a whole may be very different from the properties of its individual components. However, understanding a network at the systems level not only requires knowledge about the components of the network, but also the interactions between them. Here, a systems biology view of the rat PHD finger protein 5A (Phf5a) gene was attempted; a gene previously identified as aberrantly expressed in estrogen dependent endometrial adenocarcinoma tumors from both rat and human. Phf5ais a highly conserved cysteine rich (C4HC3) zinc finger and such proteins predominantly have a role in chromatin mediated transcriptional regulation. Moreover, PHF5A is a component of the macromolecular complex spliceosome that takes part in pre-mRNA splicing and spliceosome component coding genes have previously been shown to be implicated in various cancer types and suggested to potentially be novel antitumor drugs. To derive a systems biology view, in this study, a weighted gene network was inferred from a list of genes having correlated expression profiles to Phf5a as nodes, and common transcription factors and microRNAs regulating these genes together with annotation about biological process ontology term(s) and pathway(s) as edge weights. In the inferred network a higher weight indicates more annotation shared between two genes and, hence, the network facilitates the identification of closely interacting genes with Phf5a. The results show that highly weighted edges connect Phf5a to other spliceosome components, but also to genes involved in the metabolism of proteins, proteasome and DNA replication, repair and recombination. The results also link Phf5ato the Myc/Rb/E2F pathway, one of the central pathways associated with cancer. The proposed method for inferring a weighted gene network can easily be applied to other genes and diseases.

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Expression patterns of Phf5a/PHF5A and Gja1/GJA1 in rat and human endometrial cancer

Cited by 19 publications

References 26 publications

PHD-finger domain protein 5A functions as a novel oncoprotein in lung adenocarcinoma

PHD-finger domain protein 5A functions as a novel oncoprotein in lung adenocarcinoma

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a

A Systems Biology View of the Spliceosome Component Phf5a in Relation to Estrogen and Cancer

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