Table 1 The roles of ncRNAs in EVs in BC.

Invasion and metastasis

miR-200

–

EMT suppression promoting lung metastasis

[90]

miR-181d-5p

CDX5

CAF EVs downregulate CDX5 and HOXA5, enhancing EMT

[47]

miR-7-5p

RYK

Increased EMT transcription factor expression

[51]

miR-18b

TCEAL7

Induction of EMT through SNAIL activation

[48]

miR-1910-3p

MTMR3

Inhibition of apoptosis and autophagy activating NF-κB and WNT signalling, promoting migration

[49]

miR-221

PTEN

Enhances EMT and metastasis

[54]

miR-7641

–

Promotes invasiveness and metastasis

[50]

miR-105

ZO-1

Destruction of tight junctions in ECs, increasing vascular permeability

[56]

miR-939

VE-cadherin

Increases endothelial permeability, facilitating trans-endothelial migration of BC

[57]

SNHG16

PPAPDC1A

Sponging of miR-892b to regulate PPAPDC1A, promoting EMT, migration and invasion

[55]

miR-214

TFAP2C

Stromal EVs containing miR-214 promote metastasis following IL-6/STAT3 signalling activation

[60]

GS1-600G8.5

–

Increased BBB permeability due to downregulation of tight junction proteins

[61]

miR-181c

PDPK1

BBB breakdown through changes in actin dynamics

[62]

miR-363-5p

PDGFB

Inhibits migration and lymph node metastasis

[63]

miR-222

PDLIM2

Activation of NF-κB signalling and promotion of migration

[64]

miR-130a-3p

RAB5B

Inhibition of invasion and lymph node metastasis

[65]

miR-370-3p

FBLN5

Activation of NF-κB signalling and promotion of migration and stemness

[69]

miR-193b

RAB22A

Promotion of growth and metastasis

[66]

miR-19a

PTEN

Astrocyte EVs downregulate PTEN in BC cells promoting outgrowth of brain metastatic cells

[71]

miR-1290/miR-1246

FOXA2

Activation of astrocytes and miR-1290 promotes CNTF signalling, activating progression of brain metastases

[74]

miR-301a-3p

TIMP-2

Astrocyte interactions supporting the formation of a tumour-supportive environment in the brain

[76]

miR-503

–

XIST downregulation in BC promotes miR-503 upregulation in EVs which promote M1-M2 conversion in microglia

[77]

miR-19a

PTEN

Activation of AKT signalling and promotion of bone metastasis in ER + BC

[80]

miR-218

YY1, INHBB

Regulation of collagen deposition in osteoblasts, promoting osteolysis and facilitating bone metastasis

[81]

miR-1273g-3p

BMP3

SNHG3 regulates Bone marrow MSC differentiation in bone metastasis through miR-1273g-3p and BMP3 regulation

[82]

miR-4443

TIMP2

Upregulation of MMP-2 in the liver and primary tumour, facilitating liver metastasis

[83]

miR-122-5p

Syndecan-1

Increased cell mobility and metastatic potential

[85]

miR-200c, miR-141

–

FOXP3 induces miR-200c and miR-141 upregulation of release from BC cells, promoting distal metastasis

[87]

miR-5100

CXCL12

PGRN knockout TAMs inhibit migration and EMT through miR-5100 release and inhibition of CXCL12 signalling

[88]

miR-3613-3p

SOCS2

CAF-derived EVs promote BC invasion and metastasis through miR-3613-3p

[93]

miR-370-3p

CYLD

Fibroblast activation through BC EVs containing miR-370-3p promotes lung metastasis

[89]

miR-185-5p, miR-652-5p, miR-1246

–

BC cells promote CAF transition through miRNAs. The CAFs then promote migration of BC cells

[94]

miR-9

E-cadherin

BC cells release EVs containing miR-9 to promote CAF formation, CAFs secrete miR-9 promoting BC metastasis

[95]

miR-146a

TXNIP

miR-146a from BC cells promotes CAF transition through TXNIP regulation as well as EMT and growth in BC

[96]

miR-16, miR-148a

–

Abrogation of FAK signalling in CAFs increases miR-16 and miR-148a in EVs, reducing BC metastasis

[97]

miR-503-3p, miR-4269, miR-30e-3p

–

ELK3 expression in lymphatic ECs promotes miRNA packaging in EVs to promote metastasis in BC

[98]

miR-503

CCND2, CCND3

EVs from vascular ECs inhibit tumour growth and invasiveness in response to chemotherapy

[99]

miR-205, miR-31

UBE2N/Ubc13

MSC-derived EVs suppress migration through UBE2N/Ubc13 regulation in non-committed BC cells but promote primary tumour progression

[100]

miR-23b

MARCKS

BM-MSCs promote dormancy through regulation of MARCKS in BC cells

[101]

miR-660

KLHL21

TAM-derived EVs promote metastasis in BC through miR-660-mediated activation of NF-κB signalling

[68]

miR-138-5p

KDM6B

EVs from BC promote M2 polarisation in macrophages through KDM6B downregulation, promoting lung metastasis

[92]

circSKA3

–

Promotes invasiveness through EV transfer from invasive BC cells to less invasive BC cells

[102]

RN7SL1

–

RN7SL1 EVs activate inflammatory responses in immune cells in response to NOTCH-MYC signalling

[103]

Growth

MALAT1

–

BC EVs containing MALAT1 induce cell proliferation

[105]

miR-500a-5p

USP28

CAF-derived miR-500a-5p in EVs promotes increased proliferation and metastasis

[109]

miR-760

ARF6

M2-derived CCL18 upregulates miR-760 in BC cells which is released in EVs to promote proliferation in BC cells

[107]

miR-197

PPARG

BC stem cell EVs containing miR-197 promotes proliferation and EMT in other BC cells

[86]

NEAT1

miR-141-3p

NEAT1 in EVs from BC sponges miR-141-3p, regulating KLF12 expression, promoting growth and metastasis

[106]

miR-106a-5p

–

miR-106a-5p from MSCs accelerates cancer progression. HAND2-AS1 inhibits miR-106a-5p

[108]

miR-1-3p

GLIS1

CAF-derived miR-1-3p targets GLIS1, promoting tumour spheroid formation

[110]

miR-21, miR-34a

–

MSC-derived EVs promote BC growth

[114]

miR-222

PTEN

BC EVs containing miR-222 cause PTEN downregulation in macrophages, promoting M2 polarisation and facilitating tumour growth in vivo

[111]

miR-183-5p

PPP2CA

BC EVs containing miR-183-5p suppress PPP2CA expression in macrophages, increasing growth and metastasis

[112]

miR-142-5p, miR-183-5p, miR-222-3p

PTEN

EVs from ECs promote M2 polarisation in macrophages, promoting tumour growth

[113]

Angiogenesis

miR-182-5p

CMTM7

EVs from BC containing miR-182-5p promoted angiogenic behaviour in HUVEC cells though EGFR/AKT signalling

[115]

AC073352.1

YBX1

EVs from BC containing AC073352.1 increased angiogenic behaviour in HUVECs

[116]

miR-210

Ephrin A3 and PTP1B

Desferrioxamine-mediated induction of hypoxia in BC promotes miR-210 transfer to ECs inducing angiogenesis

[117]

miR-214

ATM

Endothelial cell-derived EVs promote endothelial cell migration through suppression of cell cycle arrest

[118]

miR-145

IRS1

EVs from BC with increased Ca²⁺ levels induce angiogenesis though PI3K/Akt signalling

[119]

miR-4488

CX3CL1

Mitochondrial calcium uniporter (MCU) enhances angiogenesis through EV miR-4488 downregulation

[120]

miR-16

VEGF

MSC-derived EVs inhibit HUVEC tube formation and migration through VEGF regulation

[121]

miR-100

mTOR

MSC-derived EVs inhibit HUVEC proliferation and migration through VEGF and HIF1α regulation

[122]

Pro-angiogenic miRNAs

–

DHA suppresses angiogenesis via increasing anti-angiogenic EVs from BC cells and decreasing pro-angiogenic miRNAs in EVs from BC cells

[123]

miR-125b

–

Wharton’s Jelly MSC EVs upregulate miR-125b in BC cells inhibits HIF1 activation, reducing angiogenesis

[124]

Drug resistance

miR-222

ERα, PTEN

Resistant BC cells and stromal cells transfer miR-222 to BC cells inducing resistance to tamoxifen, docetaxel and adriamycin

[128,129,130]

miR-222, miR-223

–

MSCs release EVs to promote quiescence and carboplatin resistance in BC

[131]

miR-887-3p

BTBD7

EVs from BC could be uptaken by other BC cells producing resistance to doxorubicin, cisplatin and fulvestrant

[132]

miR-9-5p, miR-203a-3p, miR-195-5p

ONECUT2

Chemotherapeutics cause EV release in BC cells, promoting stemness, NOTCH1, SOX9 and NANOG expression

[133]

miR-126a

–

MDSC-derived EVs induce angiogenesis and Th2 cell responses in response to doxorubicin

[134]

UCA1

–

Induction of tamoxifen resistance in tamoxifen sensitive BC cells

[135]

AGAP2-AS1

–

Induction of resistance to Trastuzumab in BC

[136]

H19

–

Doxorubicin resistance through transfer of EVs to sensitive BC cells

[137]

NEAT1

miR-141-3p

NEAT1 transfer to BC cells promotes resistance to cisplatin, paclitaxel and 5-FU through KLF1 regulation

[106]

Circ_UBE2D2

miR-200a-3p

Resistance to tamoxifen in BC cells by sponging miR-200a-3p

[139]

Circ-MMP11

miR-153-3p

Sponging miR-153-3p regulates Anilin, promoting Lapatinib resistance in BC cells

[140]

miR-134

–

Regulation of Bcl-2 increasing sensitivity to cisplatin

[141]

miR-770

STMN1

Overexpression increases Doxorubicin sensitivity. miR-770 packaged into EVs and transported to TAMs, promoting M1 polarisation

[142]

miR-342-3p

ID4

MSC-derived EVs transfer miR-342-3p to BC tissues, suppressing migration and increasing sensitivity to doxorubicin, fluorouracil and cisplatin

[143]

Metabolism

circCARM1

miR-1252-5p

BC stem cell-derived EVs cause increased expression of glycolytic enzymes in tumours

[144]

HISLA

PHD2

HISLA from TAMs stabilizes HIF1α by binding to PHD2, preventing degradation, driving metabolic reprogramming

[138]

miR-503-3p

DACT2

Macrophage EVs regulate DACT2, upregulating WNT signalling to promote glycolysis and reduce oxidative phosphorylation

[145]

SNHG3

miR-330-5p

CAF-derived SNHG3 suppresses miR-330-5p in BC cells, upregulating pyruvate kinase and glycolytic activity

[146]

miR-105

MXI1

BC EVs downregulate the MYC antagonist MXI1 in CAFs, leading to metabolic reprogramming

[147]

miR-122

PKM2

EVs from BC with miR-122 suppress glucose metabolism in primary tumours and brain and lung tissues

[148]

miR-122

PKM2

EVs from BC cells alter insulin signalling in pancreatic islet β cells, increasing systemic glucose levels

[149]