Oncotarget

Research Papers:

PLAGL1 gene function during hepatoma cells proliferation

Ana F. Vega-Benedetti, Cinthia N. Saucedo, Patrizia Zavattari, Roberta Vanni, Felix Royo, Francisco Llavero, José L. Zugaza and Luis A. Parada _

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Oncotarget. 2018; 9:32775-32794. https://doi.org/10.18632/oncotarget.25996

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Abstract

Ana F. Vega-Benedetti1, Cinthia N. Saucedo1, Patrizia Zavattari2, Roberta Vanni2, Felix Royo3, Francisco Llavero4,5,6, José L. Zugaza4,5,6 and Luis A. Parada1

1Institute of Experimental Pathology, CONICET-UNSa, Salta, Argentina

2Biochemistry, Biology and Genetics Unit, Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato SP 8, Monserrato, Cagliari, Italy

3CIC BioGUNE-CIBERehd, Bizkaia Technology Park, Derio, Spain

4Achucarro Basque Center for Neuroscience, UPV/EHU Technology Park, Leioa, Spain

5Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Spain

6IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

Correspondence to:

Luis A. Parada, email: lparada@unsa.edu.ar

Keywords: PLAGL1; hepatocellular carcinoma; cell proliferation; chromosome; methylation

Received: March 26, 2018     Accepted: July 31, 2018     Published: August 28, 2018

ABSTRACT

Hepatocellular carcinoma develops as a multistep process, in which cell cycle deregulation is a central feature, resulting in unscheduled proliferation. The PLAGL1 gene encodes a homonym zinc finger protein that is involved in cell-proliferation control. We determined the genomic profile and the transcription and expression level of PLAGL1, simultaneously with that of its molecular partners p53, PPARγ and p21, in cell-lines derived from patients with liver cancer, during in vitro cell growth. Our investigations revealed that genomic and epigenetic changes of PLAGL1 are also present in hepatoma cell-lines. Transcription of PLAGL1 in tumor cells is significantly lower than in normal fibroblasts, but no significant differences in terms of protein expression were detected between these two cell-types, indicating that there is not a direct relationship between the gene transcriptional activity and protein expression. RT-PCR analyses on normal fibroblasts, used as control, also showed that PLAGL1 and p53 genes transcription occurs as an apparent orchestrated process during normal cells proliferation, which gets disturbed in cancer cells. Furthermore, abnormal trafficking of the PLAGL1 protein may occur in hepatocarcinogenesis.


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