Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon.
Int J Mol Sci. 2022 Jul 28;23(15):8351. doi: 10.3390/ijms23158351.
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.
乳腺癌（BC）最近已成为全球最常见的癌症类型，转移性疾病是导致疾病死亡的主要原因。这就需要采取早期检测策略，特别是利用各种体液中发现的微创生物标志物。外泌体被提出为新型细胞外囊泡，可在体液中轻易检测到，由 BC 细胞或 BC 肿瘤微环境细胞分泌，并可通过各种货物分子远距离传递细胞信号。这些货物由不同的生物分子组成，其中包括新型非编码基因组产物，如 microRNAs（miRNAs）、长链非编码 RNA（lncRNAs）和最近发现的环状 RNA（circRNA），所有这些都被发现与 BC 病理学有关。在这篇综述中，将讨论 BC 衍生的外泌体中 ncRNA 货物的多种作用，阐明它们在不同水平的 BC 肿瘤进展、药物敏感性/耐药性中的主要致癌作用以及额外的肿瘤抑制作用，并展示其诊断、预后和预测生物标志物潜力。最后，利用 lncRNA 和 circRNA 的 miRNA 海绵作用机制，我们从已经发表的 BC 外泌体 ncRNA 中建立了一个经过实验验证的乳腺癌外泌体非编码 RNA 调节的靶基因轴。由此产生的基因、途径、基因本体（GO）术语和京都基因与基因组百科全书（KEGG）分析可以作为更好地理解 BC 的起点，并可能为开发新的诊断和预后生物标志物和治疗方法铺平道路。
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