DEFINING THE MECHANISMS THROUGH WHICH ALDH1A3-INDUCED LONG NONCODING RNA NRAD1 REGULATES GENE EXPRESSION IN BREAST CANCER

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor patient prognoses, owing partially to its enrichment in cancer stem cells (CSCs). Therapies targeting CSCs within TNBCs, therefore, represent enticing treatment strategies. Accordingly, long non-coding RNAs (lncRNAs) are known to confer CSC attributes through induction of stemness-associated genes by interacting with regulatory proteins and microRNAs (miRNAs). The abrogation of CSC-associated lncRNAs may therefore exemplify a mechanism through which the CSCs in TNBC tumors can be targeted. Herein, we investigate the mechanisms through which CSC-enriched long noncoding RNA NRAD1 regulates gene expression in TNBC by exploring its interactions with proteins and miRNAs. NRAD1-directed proteomics assays and RNA immunoprecipitation identified S100A8 as a possible NRAD1 binding protein in TNBC cells. Further, using miRNA microarrays, we identified changes in miRNA expression following NRAD1 knockdown in TNBC cells and elucidated miRNAs with which NRAD1 may interact to regulate gene expression.