Laura Boldrini et al., P2X7 mRNA expression in non?small cell lung cancer: MicroRNA regulation and prognostic value. Oncology Letters

Authors: Laura Boldrini, Mirella Giordano, Greta Alì, Franca Melfi, Gaetano Romano, Marco Lucchi, Gabriella Fontanini

Affiliations:
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy,
Unit of Pathological Anatomy III, University Hospital of Pisa, Pisa 56126, Italy,
Unit of Thoracic Surgery, University Hospital of Pisa, Pisa 56126, Italy.

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.

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