Prohibitin expression deregulation in gastric cancer is associated with the 3' untranslated region 1630 C>T polymorphism and copy number variation

Mariana Ferreira Leal; Priscila Daniele Ramos Cirilo; Tatiane Katsue Furuya Mazzotti; Danielle Queiroz Calcagno; Fernanda Wisnieski; Samia Demachki; Margarita Cortes Martinez; Paulo Pimentel Assumpção; Roger Chammas; Rommel Rodríguez Burbano; Marília Cardoso Smith

doi:10.1371/journal.pone.0098583

Prohibitin expression deregulation in gastric cancer is associated with the 3' untranslated region 1630 C>T polymorphism and copy number variation

PLoS One. 2014 May 30;9(5):e98583. doi: 10.1371/journal.pone.0098583. eCollection 2014.

Affiliations

¹ Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
² Laboratório de Oncologia Experimental, Departamento de Radiologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brazil.
³ Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil.
⁴ Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
⁵ Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil.
⁶ Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.

Abstract

PHB is a reported oncogene and tumor suppressor in gastric cancer. Here, we evaluated whether the PHB copy number and the rs6917 polymorphism affect its expression in gastric cancer. Down-regulation and up-regulation of PHB were observed in the evaluated tumors. Reduced expression was associated with tumor dedifferentiation and cancer initiation. The T allele of the rs6917 polymorphism was associated with reduced PHB mRNA levels. Moreover, the up-regulation of PHB appeared to be regulated by the gain of additional gene copies. Thus, PHB copy number variation and differential expression of the rs6917 polymorphism may play a role in PHB transcriptional regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics*
Alleles
Cell Differentiation / genetics
DNA Copy Number Variations / genetics*
Down-Regulation / genetics
Female
Gene Expression Regulation, Neoplastic / genetics*
Genetic Predisposition to Disease / genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Prohibitins
RNA, Messenger
Repressor Proteins / genetics*
Stomach Neoplasms / genetics*
Up-Regulation / genetics

Substances

3' Untranslated Regions
PHB protein, human
Prohibitins
RNA, Messenger
Repressor Proteins

Grants and funding

This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; RC, MACS and RRB) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; MFL, PDRC and DQC) as grants and fellowship awards. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.