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Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma

Authors: Laura Boldrini, Mirella Giordano, Cristina Niccoli, Franca Melfi, Marco Lucchi, Alfredo Mussi, Gabriella Fontanini

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

MiRNAs are vital in functioning as either oncogenes or tumor suppressors in the cell cycle. Target transcripts for immune checkpoint molecules such as PD-1/PD-L1 and (programmed cell death-1/its ligand and cytotoxic T-lymphocyte antigen 4) have proven to be beneficial against several solid tumors, including lung adenocarcinoma.

Methods

Simultaneous quantification of the expression level of miR-33a and PD-1, PD-L1 and CTLA4 mRNAs with NanoString technology was performed in 88 lung adenocarcinoma specimens. A cohort of 323 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database was further analyzed, in order to test our hypothesis. Potential interference of PD-1, PD-L1 and CTLA4 gene expression by miR-33a was predicted using the microRNA target prediction program RNA22.

Results

High miR-33a expression was significantly associated with younger (p = 0.005), female (p = 0.04), patients with low grade (p < 0.0001), early stage (p = 0.03) tumors, and better survival. The hypothesis of the involvement of miR-33a in PD-1/PD-L1/CTLA4 mechanisms was corroborated by the finding of putative miR-33a binding sites in all three genes using the RNA22 method. We found an inverse correlation between miR-33a and PD-1 levels (p = 0.01), as well as for PD-L1 (p = 0.01) and CTLA4 (p = 0.03) expression, and a significant better prognosis for patients with high miR-33a/low PD-1. TCGA database analysis confirmed that miR-33a high levels were associated with low PD-1 expression and with longer survival on a larger population.

Conclusions

Our study emphasizes the notion of a potential value of miR-33a as a favorable prognostic marker through PD-1 regulation.
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Metadata
Title
Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma
Authors
Laura Boldrini
Mirella Giordano
Cristina Niccoli
Franca Melfi
Marco Lucchi
Alfredo Mussi
Gabriella Fontanini
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0474-y

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