The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

Abstract

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Extracellular Vesicle-Related Non-Coding RNAs in Hepatocellular Carcinoma: An Overview

“…The exosomal lncSENP3-EIF4A1 exhibits reduced expression in HCC patients compared to healthy controls [11]. Both in vitro and in vivo studies have demonstrated that the introduction of SENP3-EIF4A1 functions as a tumor suppressor, inhibiting the proliferation and migration of HCC cells and acting as a competitor of the miR-9-5p target [114].…”

“…Subsequently, early endosomes integrate active molecules and other substances forming multiple intraluminal vesicles (ILVs). Late endosomes mature into multivesicular bodies (MVBs), which can encapsulate cargoes derived from various organelles, including the trans-Golgi network (TGN) and endoplasmic reticulum (ER) compartments [11]. Subsequently, MVBs can fuse with lysosomes [12], and their content becomes degraded; some degradation products, such as amino acids, are made available for reuse by the cell.…”

Hydrogel-encapsulated extracellular vesicles for the regeneration of spinal cord injury

“…EVs contribute to tissue repair and regeneration and immunosurveillance. Subtypes of EVs are microvesicles, exosomes, and apoptotic bodies, which are classified depending on their biogenesis, release pathways, and size ( Samanta et al, 2018 ; Rezaee et al, 2023 ). EVs derived from different types of cells promoted functional recovery after SCI through their neuroprotective and neuroregenerative properties ( Romanelli et al, 2019 ).…”

The role of non-coding RNAs in extracellular vesicles in breast cancer and their diagnostic implications

“…EV-mediated transfer of ncRNAs from resistant cancer cells to sensitive cells is an important mechanism for propagation of tumour drug resistance. This topic has been reviewed deeply, in a 2021 systematic review exploring the role of EV-carried miRNAs in the induction of chemoresistance in multiple cancer types [ 125 ], and in recently published BC focused reviews by Weon Yi [ 126 ] and Rezaee et al [ 127 ].…”