Table 2 Exosomal miRNAs as prognostic and predictive biomarkers

Lung cancer

miR-155/ -146a

Immune cells

Immune cells

HO1/ IRAK1 and TRAF6

TP532NP1

MiR-155 enhances while miR-146a reduces inflammatory gene expression. Promotes endotoxininduced inflammation.

Inflammation

[10]

/

Mast cell

KIT-SCF/ PI3K

/

Enhances proliferation in recipient tumor cells.

Proliferation

[100]

miR-210

Lung adenocarcinoma

Stromal cells

Ephrin A3

Promotes angiogenesis.

Angiogenesis

[52]

miR-21

Bronchial epithelial (HBE) cells

Normal HBE cells

STAT3

Increases VEGF levels in recipient cells, which is involved in angiogenesis and malignant transformation of HBE cells.

Angiogenesis

[53]

miR-192

A549

Endothelial cells

ICAM-1/ PTPRJ

Regulates non-cell-autonomous invasiveness, and tumor-induced osteoclastogenesis.

Bone metastasis

[100]

miR-494

Lung adenocarcinoma cells

Lymph nodes, lung cells

MAL,cdh17

/

Pre-metastasis

[101]

miR-542-3p

cdn17, TRAF4

miR-23b-3p, miR-10b-5p and miR-21-5p

Plasmatic exosomes

Non-small cell lung cancer cells(NSCLC)

/

/

Progression, angiogenesis and metastasis

[102, 103]

Digestive system

Digestive tract

Esophageal cancer(ESCC)

miR-30a

ESCC cells

/

WNT2/FZD2

Down-regulation of miR-30a-3p/5p expression is correlated with the activation of Wnt signaling in ESCC, which enhances cell proliferation.

Proliferation

[104]

Gastric cancer

miR-21

Macrophage

BGC-823

PDCD4

MiR-21 inhibitor-loaded exosomes promote migration and reduce apoptosis.

Metastasis

[57]

miR-221

Mesenchymal stem cells

HGC-27

/

Promotes HGC-27 growth and migration.

Metastasis

[105]

Colorectal cancer(CRC)

miR-21, −192 and − 221

HCT-15, SW480 and WiDr

HepG2 and A549

/

Regulate the expression of target genes in HepG2 and A549 cells. May promote various functions.

/

[73]

Let-7a

CRC cells

T cells

/

Let-7a expression is positively associated with cancer-specific mortality, and T cells low expresion.

Inmmue inhibitor

[106]

miR-19a

CRC cells

/

PTEN

Over-expression was significantly associated with poorer survival.

Metastasis

[76]

miR-23b-3p

Blood plasma isolated from CRC patients

Colon cancer cells

/

/

Inhibitor

[103]

Digestive gland

Liver cancer

miR-142 and − 223

Macrophages

Hepatocellular carcinoma cells (HuH7 and HepG2)

Stathmin-1/ IGF1R

Inhibits proliferation of cancer cells.

Inhibitor

[77]

miR-122

Huh7 cells

HepG2 cells

IGF1R mRNA

Reduced growth and proliferation of recipient HepG2 cells.

Inhibitor

[107]

miR-584

Hep3B, HepG2, and PLC/PRF/5

Hep3B, HepG2 and PLC/PRF/5

TGF-β activated kinase-1 (TAK1)

HCC cell-derived exosomes modulate TAK1 expression and associated signaling. They also enhance the growth of transformed recipient cells.

Proliferation

[47]

Pancreatic cancer (PC)

miR-122-5p and miR-193b-3p

Plasma samples

Pancreatic cancer cells

/

Act on several molecular pathways closely related with PC such as p53 signaling pathway, TGF-beta signaling pathway and so on.

Proliferation

[108]

miR-221-3p

Inhibitor

miR-23b-3p

PANC-1 cells

PANC-1 cells

CA-19-9

miR-23b-3p expression in sera or that in the exosomes isolated from sera showed a close relationship with CA-19-9 expression.

Proliferation and metastasis

[103, 109]

miR-141, miR-375

PCa cells

Serum

/

miR-141 and miR-375 were associated with recurrent (metastatic) PCa following radical prostatectomy

metastasis

[110]

miR-1290, miR-375

PCa cells

Plasma

/

Various RNA species and changes in exosomal RNA contents are robust candidates as clinical biomarkers for advanced PCa

Survival prognosis

[111]

miR-19b

PCa cells

Urine

/

Active secretion of miR-19b containing vesicles by tumor cells

Diagnosis

[112]

Isomirs of miR-21, miR-375 and miR-204

PCa cells

Urine

MARCKS, BTG2, PTEN, RECK

The miRNA-read-length of miR-204, miR-21 and miR-375 showed clear differences when comparing controls with PCa patient samples.

Progression

[113, 114]

miR-141

PCa cells

Serum

/

Exosomal miR-141 is upregulated in the serum from patients with PCa compared with patients with benign prostate hyperplasia or the healthy volunteers

Metastasis

[115]

miR-200c-3p

Urine

PCa cells

ZEB1, ZEB2, SNAIL2

miRNA re-expression inhibits prostasphere formation, decreases clonogenic survival, and reduces NOTCH1 and LIN28B gene expression, the drivers of self-renewal.

Suppressor

[114, 116]

miR-21-5p

Urine

PCa cells

MARCKS, BTG2, PTEN, RECK

Blocking miRNA with antisense oligonucleotides has no effect on cell proliferation, but it leads to increased sensitivity to apoptosis and the inhibition of cell motility and invasion

Progression

Let-7c

Urine

PCa cells

E2F2 and CCND2, LIN28, MYC, EZH2

miRNA family are down-regulated in PCa.

Suppressor

miR-196a-5p

Urine

PCa cells

ETS-related gene (ERG)

The high levels of miR-196a-5p in normal prostate cells help to maintain the levels of ERG low.

Metastasis

[117]

miR-501-3p

Urine

PCa cells

E-cadherin

miR-501-3p promoted the invasiveness of pancreatic ductal adenocarcinoma cells possibly by suppressing E-cadherin

miR-2909

Urine

PCa cells

/

miR-2909 levels were only increased in urinary exosome from PCa patients

Metastasis

[118]

miR-145

Urine

PCa cells

KRAS, ERK5, KLKs, FSCN1, SWAP70, MMP-13, GOLM1, FNDC3B, CD133, CD44, OCT4, MYC, KLF4

Urinary levels of exosomal miR-145 were increased in PCa patients vs BPH patients

Suppressor

[114, 119]

miR-1246

Serum

PCa cells

/

Serum levels of exosomal miR-1246 were increased in PCa patients vs BPH patients

Metastasis

[120]

Cholangiocarcinoma

/

KMBC and HuCCT1

Mesenchymal stem cells

/

Enhance MSC migratory capability and expression of alpha-smooth muscle actin mRNA. Promote the release of CXCL-1, CCL2, and IL-6.

Metastasis

[121]

Bladder cancer

Exosome-derived miR- 29c

miR-29c

BIU-87 cells

BCL-2 and MCL-1

Exosome-derived microRNA29c induces apoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1.

Apoptosis

[78]

Reproductive system

Female

Breast cancer

miR-105

MDA-MB-231

Endothelial cells

Protein ZO-1

Destroys tight junctions and the integrity of natural barriers to metastasis.

Metastasis

[58]

miR-10b

MDA-MB-231

HMLE (MCF-7)

HOXD10/KLF4

Induces invasion of non-malignant HMLE cells.

Metastasis

[122]

miR-210

MDA-MB-231

4 T1

Endothelial cells

/

Suppresses expression of specific target genes resulting in enhanced angiogenesis.

Metastasis

[123]

miR-503

Endothelial cells

Breast cancer cells

CCND2/ CCND

Alters proliferation and invasion.

Metastasis

[124]

miR-16

EGCG-treated 4 T1 cells

Macrophages

/

Inhibits TAM infiltration and M2 polarization.

Metastasis

[125]

miR-16

Mesenchymal

stem cells

4 T1

VEGF mRNA

Down-regulates the expression of vascular endothelial growth factor (VEGF) in tumor cells.

Metastasis

[126]

miR-140

Pre-adipocyte

(3T3L1)

MCF10

SOX9

Regulates differentiation, stemness, and migration.

Metastasis

[127]

miR-122

Breast cancer patients/ MCF10A

Recipient pre-metastatic niche cells

PKM2 and GLUT1

Suppresses glucose uptake by niche cells by down-regulating pyruvate kinase

Metastasis

[128]

Hepatoma cells (Huh-7 and Hep3B cells)

MCF-7 cells

SDC1

The liver-derived exosomes increased the mobility of breast cancer MCF-7 cells though SDC1 downregulation mediated by exosomal miR-122-5p.

Metastasis

[60]

miR-23b

Bone marrow mesenchymal stem cells

Breast cancer cells

MARCKS

Decreases MARCKS expression and promotes breast cancer cell dormancy in the metastatic niche.

Dormancy

[129]

miR-127, −197, −222, and − 223

Bone marrow stroma

MDA-MB-231

CXCL12

Reduce CXCL12 levels and decreases proliferation. Elicit dormancy in bone marrow metastases in breast cancer.

Dormancy

[79]

miR-134

Hs578T and Hs578Ts(i)8

Breast cancer cells

STAT5B

Reduces STAT5B and Hsp90 expression. Decreases cell migration and invasion.

Drug resistance

[130]

miR-221/ -222

MCF-7 (Tamoxifen resistant)

MCF-7 (Tamoxifen-sensitive)

P27 and ERα

Enhances tamoxifen resistance in recipient cells.

Drug resistance

[68]

miR-223

IL-4-activated macrophages

MDA-MB-231

Mef2c- β-catenin

Promotes the invasion of breast cancer cells.

Metastasis

[131]

miR-124/ -145

Mesenchymal stem cells

Glioma cells and glioma stem cells

SCP-1/Sox2

Decrease the migration of glioma cells and the self-renewal of glioma stem cells.

Proliferation

[132]

miR-21/ -3a

Bone marrow-derived MSCs

Breast cancer cells

TPM1/PDCD4/ Bcl-2

Elicit pro-tumorigenic and anti-apoptotic effects.

Proliferation

[133]

miR-200

Metastatic breast cells

Non-metastatic breast cells

ZEB1/ZEB2

Suppress the EMT and enhance the reverse process, mesenchymal-to-epithelial transition (MET) by inhibiting the expression of Zeb1 and Zeb2.

Metastasis

[134]

MiR-373

breast cancer cells

/

/

downregulate the protein expression of ER and inhibit apoptosis induced by camptothecin.

Malignant prediction

[66]

Ovarian cancer

miR-200a/b/c/141

SKOV-3 and OVCAR-3

Ovarian cancer cells (OC)

ZEB1 (TCF8/ZFHX1A/δEF1) and ZEB2 (SIP1/ZFHX1B/SMAD1P1)

Down-regulation of miR-200 in mesothelial cells promotes cancer cell attachment and proliferation.

Proliferation

[55]

let-7 family

SKOV-3

OVCAR-3

/

Exosome release varies between ovarian cancer cell lines and is correlated with invasive potential.

Metastasis

[96]

miR-21-5p

CP70

A2780

NAV3

Increases platinum-resistance in A2780 cells.

Drug resistance

[135]

ATF2, MTA1, and ROCK1/2

High-grade ovarian cancer

Endothelial cells

/

Exosomes derived from high-grade ovarian cancer alter angiogenesis compared to non-high-grade ovarian cancer cells.

Metastasis

[136]

miR-24-3p, −891a, and -106a- 5p

The serum of patients with NPC or TW03 cells

T-cell

MARK1

Alter T-cell proliferation and differentiation.

Metastasis

[137]

miR-127-3p

/

OVCAR-3 and Caov-3 cells

Bcl-associated athanogene 5 (BAG5) gene

Inhibits the BAG5 gene, and subsequent BAG5 upregulation ameliorated the tumor-suppressive effects of miR-127-3p overexpression in OC.

Proliferation

[138]

OC ES-2 cells

Endothelial cells

PPP1CA

The upregulation of PPP1CA in OC is attributed to the downregulation of hsa-miR-127-3p.

Proliferation

[139, 140]

miR-339-5p

OC ES-2 cells

Endothelial cells

WNT (CHD8)

CHD8 inhibits the transcription of β-catenin target genes through chromatin compaction and it may be a tumor suppressor gene. Overexpression of exosomal miR-339-3p could influence WNT3A/CHD8 pathway.

Proliferation and metastasis

[140, 141]

miR-409-3p

OC ES-2 cells

Endothelial cells

WNT (CTBP1)

CTBP1 was demonstrated to activate the expression of Wnt genes and downregulate their downstream E-cadherin in a TCF-independent manner. Overexpression of exosomal miR-409-3p could influence WNT7A/CTBP1 pathway.

Proliferation and metastasis

[140, 142]

Male

Prostate cancer (PC)

MiR-141

Bone metastatic PCa cells

Bone cells

NF-κB signaling

Serum exosomal expression of miR-141 were associated with T-classification and metastasis.

Metastasis

[143]

miR-375

Serum

PC cells

/

miR-375 is associated with recurrent (metastatic) PCa following radical prostatectomy

Metastasis

[111]

miR-34a

Docetaxel-resistant PC cells

Docetaxel-resistant

B-cell Lymphoma 2

Influences cell response to docetaxel in prostate cancer cells through regulation of anti-apoptotic BCL-2.

Drug resistance

[74]

miR-125a

DIAPH3-silenced cells

macrophages

AKT1

Suppresses AKT1 expression and proliferation of cancer.

Proliferation

[48]

miR-290,-378

PC cells

/

/

Overexpression shorten prostate cancer overall survival.

Prognosis

[67]

miR-1290

Plasma

/

/

Correlation with overall survival

Prognosis

[111]

miR-19b

Urine

/

/

Correlation with overall survival

Prognosis

Neuroblastoma

miR-21

NBL cells

Human monocytes

TLR8-NF-кB

/

Drug resistance

[143]

miR-155

Monocytes

NBL cells

TERF1

Hematological malignancies

miR-210

K562 under hypoxic conditions

Umbilical vein endothelial cells

EFNA3

Exosomal miRNAs derived from cancer cells under hypoxic conditions may affect angiogenic activity in endothelial cells.

Metastasis

[90]

miR-126

LAMA84

Endothelial cells

CXCL12 and VCAM1

HUVECs with a miR-126 inhibitor reversed the decrease in CXCL12, restores motility and adhesion in LAMA84 cells.

Metastasis

[144]

miR-202-3p

Chronic lymphocytic leukemia (MEC1)

Human stromal cells

c-Fos and ATM

Enhances proliferation of recipient cells.

Proliferation

[145]

miR-92a

K562 cells

Umbilical vein endothelial cells

Integrin α5

Enhances endothelial cell migration and tube formation.

Metastasis

[146]

miR-21

CLL cells

MSCs and endothelial cells

/

Induce differentiation of stromal cells into cancer-associated fibroblasts.

Metastasis

[147]

miR-135b

Multiple myeloma cells

endothelial cells

FIH-1

Exosomal miR-135b from HR-MM cells enhances endothelial tube formation under hypoxic conditions via the HIF-FIH signaling pathway.

Metastasis, angiogenesis

[148]

Melanoma

miR-125b

PLX4032-resistant melanoma cell line

Primary melanoma cell lines

apoptotic pathways

miRNA inhibitors increased the fraction of apoptotic cells in LM16-R cells

Metastasis

[149]

miR-31, − 185, and -34b

A375 and SK-MEL-28

Normal melanocytes

HAPLN1, GRP78

/

Metastasis

[150]

miR-222

Metastatic melanoma cell lines

Primary melanoma cell lines

p27Kip1

Activates the PI3K/AKT pathway.

Metastasis

[151]

Merkel Cell Carcinoma (MCC)

miR-30a, miR-34, miR-142-3p, miR-1539

MCV-positive or -negative tumors

/

/

Upregulation when discriminating between MCPyV-negative and MCPyV-positive MCCs

MCPyV infection

[63, 152]

miR-181d

Downregulation when discriminating between MCPyV-negative and MCPyV-positive MCCs