title: P2X7 mRNA expression in non-small cell lung cancer: MicroRNA regulation and prognostic value.
abstract: The human P2X7 receptor is significant and exhibits several functions in neoplasia. At present, little is known with regard to its regulation. P2X7 expression may be regulated post-transcriptionally and putative microRNA (miRNA) binding sites are considered to be involved. The aim of this study was to determine whether miRNAs (miR-21, let-7 g and miR-205) regulate P2X7 mRNA stability. In addition, the impact of P2X7 expression in patients with non-small cell lung cancer (NSCLC) was investigated. P2X7 mRNA and mature Let-7 g, miR-21, and miR-205 expression levels were quantified in 96 NSCLC cases using quantitative reverse transcription polymerase chain reaction. In all samples, epidermal growth factor receptor and K-Ras mutational analysis was also performed. Samples with low P2X7 expression were found to exhibit a higher fold change in miR-21 expression when compared with samples exhibiting high P2X7 expression. Significantly higher miR-21 expression was observed in the tumors of NSCLC patients with a K-Ras mutation when compared with patients who had K-Ras wild-type tumors (P=0.003). Additionally, to evaluate the association between P2X7 expression and prognosis in NSCLC patients, survival analysis was performed using the Kaplan-Meier method. A significant difference in the progression-free survival and overall survival in the NSCLC patients with high P2X7 expression was identified, when compared with that of patients with low expression (P=0.03 and P=0.02, respetively). Therefore, we hypothesized that high levels of miR-21 expression in NSCLC patients with K-Ras mutations may be regulated by a complex circuit, including P2X7 downregulation and together these processes may promote tumor progression.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Unit of Pathological Anatomy III, University Hospital of Pisa, Pisa 56126, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Alì
authors.affiliation: Unit of Thoracic Surgery, University Hospital of Pisa, Pisa 56126, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Melfi
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Romano
authors.affiliation: Unit of Thoracic Surgery, University Hospital of Pisa, Pisa 56126, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
keywords: P2X7; miRNA; non-small cell lung cancer; prognosis