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.

P2X7 mRNA expression in non-small cell lung cancer: MicroRNA regulation and prognostic value

BOLDRINI, LAURA;Giordano M;Alì G;Melfi F;Romano G;LUCCHI, MARCO;FONTANINI, GABRIELLA
2015-01-01

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.
2015
Boldrini, Laura; Giordano, M; Alì, G; Melfi, F; Romano, G; Lucchi, Marco; Fontanini, Gabriella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/662466
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