SRA

The overexpression of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) is an important cause of poor outcome and its expression is able to predict the progression-free and overall survival in patients receiving platinum-containing chemotherapy. Recently, we have demonstrated APE1 involvement in miRNA biogenesis related to cancer progression. Overall design: In this work, through the use of NGS and Nanostring strategies, we report the identification of miRNAs that are modulated in lung cancer cells upon APE1 silencing. We defined a miRNA signature consisting of the 13 miRNAs, which strongly correlates with APE1 expression in lung cancer: miR-1246, miR-4488, miR-24, miR-183, miR-660, miR-130b, miR-543, miR-200c, miR-376c, miR-218, miR-146a, miR-92b and miR-33a. Gene ontology annotation and pathway analysis of the miRNA signature revealed its biological significance in cancer proliferation and survival. Among the miRNAs regulated by APE1, miRNA-33a-5p targets DICER, a major miRNA biogenesis gene whose expression is found to be downregulated in several tumours. We here validated DICER as a direct functional target of miR-33a and profiled miR-33a, DICER and APE1 expression in clinical samples.