APE1 controls DICER expression through functional regulation of miRNA33a: a novel hypothesis for NSCLC cancer progression [RNA-Seq]

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. 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.