The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications

Abstract

Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20–23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

Keywords:

• breast cancer
• tumor microenvironment
• exosome
• miRNAs
• detection
• therapy

Abbreviations

BMSCs, bone marrow mesenchymal stem cells; BC, breast cancer; BCBM, breast cancer brain metastasis; CSCs, cancer stem cells; CAFs, cancer-associated fibroblasts; CTCs, circulating tumor cells; EMT, epithelial-mesenchymal transition; ER, estrogen receptor; EFS, event-free survival; ECM, extracellular matrix; FAK, focal adhesion kinase; HUCMSCs, human umbilical cord-derived MSCs; IBSP, integrin-binding sialoprotein; LN, lymph node; MRI, magnetic resonance imaging; MHC, major histocompatibility complex; MMP, matrix metalloproteinase; MSCs, mesenchymal stem cells; MVBs, multiple vesicular bodies; MDSC, myeloid-derived suppressor cells; ncRNAs, non-coding RNAs; NFs, normal fibroblasts; PDGF, platelet-derived growth factor;PARP, poly(ADP-ribose) polymerase; PFS, progression-free survival; RIBE, radiation-induced bystander effect; TNBC, triple-negative breast cancer; TME, tumor microenvironment; TAMs, tumor-associated macrophages; US, ultrasound.

Acknowledgments

Jie Li, Dejiao He and Yajun Bi are co-first authors for this study. We thank the institute for providing the funding and the individuals for offering help during the manuscript process.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declare that there is no conflict of interest in this work.

Additional information

Funding

This work was supported by Nature Science Foundation of Hubei Province (2020CFB685).