The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer

Abstract

Breast cancer, ranking first among women’s cancers worldwide, develops from the breast tissue. Study of the breast tissue is, therefore of great significance to the diagnosis and treatment of breast cancer. Exosomes, acting as an effective communicator between cells, are in the ascendant in recent years. One of the most important cargoes contained in the exosomes is microRNAs, belonging to the non-coding RNA family. When the exosomal microRNAs are absorbed into the intracellular location, most of the microRNAs will act as tumor promoters or suppressors by inhibiting the translation process of the target mRNA, thus affecting the behavior of other stromal cells in the tumor microenvironment. At present, growing research focuses on the different types of donor cell sources, their contribution to cancer, miRNA profiling, their biomarker potential, etc. This review aims to state the function of diverse miRNAs in exosomes medicated cell–cell communication and the potency of some specific enriched miRNAs as molecular markers in clinical trials. We also describe the mechanism of anti-cancer compounds through exosomes and the exploration of artificially engineered techniques that lead miRNA-inhibitors into exosomes for therapeutic use.

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

“…MicroRNAs (miRNAs) are a group of noncoding singlestranded short RNA molecules composed of 19-25 nucleotides that serve as regulators of gene expression. 33 A miRNA can recognize and bind directly to the complementary site of the 3 0 -UTR of one or more target mRNAs, resulting in transcriptional repression and/or degradation of the target mRNA. 34,35 Many miRNAs are abnormally expressed in ESCC tissues and may drive the progression of this disease, such as miR-135, miR-214, miR-6775-3p.…”

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

“…A combination of miRNAs and long non-coding RNAs (lncRNAs) that exist in the exosomes exert pro-angiogenic function by reprogramming the target cell [25,38]. Most notably, miRNA-126α, from MDSC-derived exosomes and tumor-derived exosomes (TEXs), was able to sustain MDSCs and promote angiogenesis, while conveying chemoresistance [25,38,80,81]. Specifically, miR-155 and miR-21 induced MDSCs in the TME to acquire a more immunosuppressive function, while simultaneously facilitated tumor growth via activation of the STAT3 pathway [25,64].…”

“…Specifically, miR-155 and miR-21 induced MDSCs in the TME to acquire a more immunosuppressive function, while simultaneously facilitated tumor growth via activation of the STAT3 pathway [25,64]. miR-9 contained in MDSC-derived exosomes and TEXs was shown to increase the immunosuppressive activity of MDSC and promote angiogenesis by reprogramming endothelial cells [49,81]. Moreover, the HOX transcript antisense intergenic RNA (HOTAIR) was also associated with tumor growth and angiogenesis, as well as for the CCL2-mediated recruitment of MDSCs and TIMs (namely, TAMs) [82].…”

Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells

“…Several studies revealed that these exosomal miRNA are implicated in cancer research, as tumor cells secrete different microRNAs capable of initiating cross-talk with the adjacent tumor microenvironment and educate them for adapting tumor favoring conditions for cancer progression [129,[241][242][243][244][245]. Many exosomal miRNA were intensively studied for their ability to promote tumor progression by indicating drug resistance (miR-9,mir 221/222,miR 1246),metabolic reprogramming in CAF cells(miR105), intimating angiogenesis in endothelial cells(miR105, miR210), tumorigenesis in epithelial cells (miR10b, miR10a, miR21), osteogenesis in MSCs(mir940) [246][247][248][249]. Moreover, these exosomal miRNA can be circulated and used as potential diagnostic and prognostic markers in breast cancer [246,250].…”

“…Many exosomal miRNA were intensively studied for their ability to promote tumor progression by indicating drug resistance (miR-9,mir 221/222,miR 1246),metabolic reprogramming in CAF cells(miR105), intimating angiogenesis in endothelial cells(miR105, miR210), tumorigenesis in epithelial cells (miR10b, miR10a, miR21), osteogenesis in MSCs(mir940) [246][247][248][249]. Moreover, these exosomal miRNA can be circulated and used as potential diagnostic and prognostic markers in breast cancer [246,250]. For example, plasma and serum samples of breast cancer patients show microRNAs such as miR-106a-3p, 106a-5p, 20b-5p, and 92a-2-5p (plasma miRNAs); miR-106a-5p, 19b-3p, and 92a-3p (serum miRNAs) can be used as potential biomarkers in BC patients [251].…”