APE1 controls DICER1 expression through functional regulation of miRNA33a and miRNA130b: a novel hypothesis for NSCLC cancer progression [NanoString]

ABSTRACT: Lung cancer is the leading cause of cancer death worldwide. The lack of specific and sensitive methods for early diagnosis as well as inadequate targeted therapies contribute to poor outcomes. A growing body of evidences suggests different roles of microRNAs including development and progression of lung cancer. The overexpression of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) is an important cause of poor chemotherapeutic 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 article, 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 downregulated by APE1 is miRNA-33a-5p which 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. Our findings suggest that APE1 may promote lung cancer progression through modulation of Dicer expression via miR-33a regulation. Our findings reveal new mechanistic insight into how APE1 functions in tumor biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166749 | GEO | 2022/08/03

REPOSITORIES: GEO