Circulating exosomal long non-coding RNAs NAMPT-Antisense and SNHG5 as emerging biomarkers in breast cancer.

Abstract

Breast cancer (BC) is the leading cause of cancer-related deaths among women globally. The regulatory role of long non-coding RNAs (lncRNAs) in tumorigenesis has emerged in various cancer types, including BC. Exosomes, acting as carriers of lncRNAs and other cargo, play a crucial role in mediating communication between cancer cells and tumor microenvironment. Nicotinamide-phosphoribosyl-transferase (NAMPT) has attracted much attention in cancer research. This study sought to explore the role of two lncRNAs interrelated with NAMPT; NAMPT-AS and SNHG5 in BC and to investigate their circulating serum exosomal levels in subjects with/without BC. Serum exosomes were isolated from BC patients and healthy controls, and the expression levels of NAMPT-AS, SNHG5 and NAMPT were measured using qRT-PCR. Serum NAMPT protein levels were quantified by ELISA. Thorough analysis of The-Cancer-Genome-Atlas (TCGA) data for BC-patients was conducted. Serum exosomal NAMPT-AS and SNHG5 levels were found to be significantly upregulated in BC patients compared to control subjects, and both of them were found to be strongly associated with each other and positively correlated with serum exosomal NAMPT. Receiver-operating-characteristics (ROC) analysis revealed that both exosomal NAMPT-AS and SNHG5 can differentiate between BC patients and control subjects. Gene-ontology, protein-protein-interaction-networks and survival analyses of TCGA data revealed distinct molecular signatures for high/low NAMPT-AS and SNHG5 BC-samples. Notably, upregulation of both lncRNAs was associated with poor prognosis and reduced overall survival. In conclusion, the results of the current study portray NAMPT-AS and SNHG5 as key interconnected molecular mediators and promising novel diagnostic/prognostic biomarkers and therapeutic targets for BC.