Spotlight on Exosomal Non-Coding RNAs in Breast Cancer: An In Silico Analysis to Identify Potential lncRNA/circRNA-miRNA-Target Axis

Abstract

Breast cancer (BC) has recently become the most common cancer type worldwide, with metastatic disease being the main reason for disease mortality. This has brought about strategies for early detection, especially the utilization of minimally invasive biomarkers found in various bodily fluids. Exosomes have been proposed as novel extracellular vesicles, readily detectable in bodily fluids, secreted from BC-cells or BC-tumor microenvironment cells, and capable of conferring cellular signals over long distances via various cargo molecules. This cargo is composed of different biomolecules, among which are the novel non-coding genome products, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the recently discovered circular RNA (circRNA), all of which were found to be implicated in BC pathology. In this review, the diverse roles of the ncRNA cargo of BC-derived exosomes will be discussed, shedding light on their primarily oncogenic and additionally tumor suppressor roles at different levels of BC tumor progression, and drug sensitivity/resistance, along with presenting their diagnostic, prognostic, and predictive biomarker potential. Finally, benefiting from the miRNA sponging mechanism of action of lncRNAs and circRNAs, we established an experimentally validated breast cancer exosomal non-coding RNAs-regulated target gene axis from already published exosomal ncRNAs in BC. The resulting genes, pathways, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis could be a starting point to better understand BC and may pave the way for the development of novel diagnostic and prognostic biomarkers and therapeutics.

Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis

“…We sought to identify shared target genes and pathways downstream of the CRC exosomal ncRNAs axis using an in silico approach as described in Ashekyan et al [ 17 ] based primarily on miRTargetlink 2.0 [ 62 ]. The utilized approach takes advantage of the sponging mechanism of action of lncRNAs and circRNAs on miRNAs, which in turn leads to relief in the inhibition exerted by the respective miRNA on the target mRNA, leading to the upregulation of the target gene.…”

“…CeRNAs can thus control the quantity of the protein encoded by a certain gene or alter the epigenetic regulation of gene expression. This interplay of miRNAs and ceRNAs is particularly important in cancer development, because it has the ability to repress or promote carcinogenesis depending on the presence of tumor suppressor genes or oncogenes on the downstream end of the target miRNA [ 17 , 18 , 19 , 20 ].…”

Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment

“…Exosomes are discoidal vesicles of 30–150 nm diameter that carry cargo derived from the host cell, such as proteins, lipids, DNA, and RNA. Exosomes carry their cargo to recipient cells, allowing immune and cancerous cells to communicate through them ( 213 , 214 ). Cancer invasion and metastasis may be facilitated by exosome-mediated interactions between cancerous cells and the TME, encouraging EMT, angiogenesis, and immune escape ( 215 ).…”

LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa

“…Furthermore, they have been shown to be involved in physiological and/or pathological biological processes ( 6 ). LncRNAs have been demonstrated to have important roles in various types of cancer, including bladder cancer ( 6 ), ovarian cancer ( 7 ), pancreatic cancer ( 8 ), breast cancer and metastasis ( 9 ). LncRNAs also fulfill roles in various degenerative conditions, including Alzheimer's disease ( 10 ), osteoarthritis ( 11 ), multiple sclerosis ( 12 ), but also in autoimmunity states, such as Sjogren's syndrome ( 13 ), autoimmune hepatitis ( 14 ) and types 1 and 2 diabetes ( 15 ).…”