Table 1.

Origin and biological effects of sEV-derived ncRNA.

Step	Molecule	Cell of Origin	Effect	Ref.
EMT	miR-301a	GBM, PC	Activation of Wnt/β-catenin signaling, suppression of TCEAL7, p63 and E-cadherin	[89,124]
	miR-92a	NSCLC	Activation of PTEN/PI3K/AKT	[90]
	miR-191	Melanoma	Activation of MAPK signaling	[14]
	miR-1260b	LC	Activation of Wnt/β-catenin signaling via inhibition of sFRP1 and Smad4	[91]
	miR-181d-5p	CAFs in BC	Suppression of CDC2 and HOXA5
	miR-23a	NSCLC	Induction of TGFβ signaling and inhibition of E-cadherin	[125]
	miR-21 miR-143 miR-378e	CAFs in BC	Upregulation of NANOG, SOX2, SNAIL and ZEB	[126]
	miR-499a-5p	LC	Activation of mTOR signaling	[127]
	miR-19b-3p	CCRCC	Downregulation of PTEN	[127]
	miR-382-5p	CAFs in OSCC	Upregulation of ß-catenin and N-cadherin	[128]
ECM degradation	miR-21	CRC, EC	MMP activation via inhibition of PDCD4 and TIMP-3	[101,102,104]
	miR-181b	HCC, ESCC	MMP activation via inhibition of TIMP-3	[105,106]
	MMP1 mRNA	OC	Enhanced MMP1 expression in recipient cells	[100]
	miR-382-5p	CAFs in OSCC	Upregulation of MMP-9 and MMP-3	[128]
Anoikis resistance	miR-210	CRC		[92]
	miR-222-3p	NSCLC	Inhibition of SOCS3	[93]
Stroma	miR-9	BC	CAF formation	[121]
	miR-211	Melanoma	CAF formation via MAPK activation	[12]
	miR-155	PDAC	CAF formation via downregulation of TP53INP1	[122]
Immune modulation	miR-24-3p, miR-891a, miR-106a-5p, miR-20a-5p, miR-1908	NPC	T-cell exhaustion via downregulation of the MARK1 signaling pathway	[129]
	miR-690, miR-677, miR-29b	Melanoma	CD4+ T-cell apoptosis, increase of caspase-3, caspase-7 and caspase-9, downregulation of BCL-2	[130]
	circUHRF1	HCC	NK dysfunction via inhibition of IFN-γ and TNF-α secretion	[131]
	miR-301a-3p	PDAC	M2 macrophage polarization via activation of PTEN/PI3Kγ signaling	[132]
	miR-378a-3p	Various cell lines	Decreased NK cytotoxicity via inhibition of granzyme B	[133]
	miR-212-3p	PDAC	DC dysfunction via PFXAP inhibition and compromised MHCII expression	[134]
	miR-150-5p, miR-142-3p	Tregs	DC exhaustion	[135]
	miR-203	PDAC	DC dysfunction via TLR4 inhibition	[136]
	miR-18a	CeC	T-cell exhaustion, suppression of PTEN, WNK2 and SOX6, and enhanced PD-L1 levels	[137]
	miR-23a	HCC	T-cell exhaustion, suppression of PTEN and enhanced PD-L1 levels	[138,139]
	miR-10a, miR-21	Glioma	MDSC expansion by targeting RAR and PTEN	[140]
	miR-1246	Mutant p53 cancer cell lines	M2 macrophage polarization via targeting TERF2IP	[141,142]
	Let7	Hypoxic tumor cells	M2 polarization and metabolic reprogramming in macrophages via suppression of AKT-mTOR signaling	[143]
	miR-29a-3p and miR-21-5p	TAMs in OC	Suppression of STAT3 in CD4 T-cells and corresponding Treg induction	[144]
	miR-125b-5p	Melanoma	M2 macrophage polarization via downregulation of LIPA	[145]
	miR-27a-3p	BC	PD-L1-mediated immune evasion via targeting MAGI2/PTEN/PI3K signaling	[146]
Intra- vasation	miR-939	BC	Downregulation of VE-Cadherin in ECs	[147]
	miR-105	BC	Downregulation of ZO-1 in ECs	[148]
	miR-181c	BC	Destruction of blood–brain barrier and promotion of brain metastasis via downregulation of PDPK1	[149]
Angio- genesis	miR-17-5p	NPC	Promoting angiogenic activity in ECs via AKT/VEGF-A expression	[115]
	Mir-155	GC	Suppression of FOXO3a and c-MYC to enhance the expression of VEGF in ECs	[150]
	miR-27a	PDAC	Proliferation of ECs via inhibition of BTG2	[13]
	miR-135b, miR-210, miR-21, miR-23a	Hypoxic tumor cells	Induction of blood vessel formation	[151,152,153]
	MALAT1	OC	Pro-angiogenic gene expression in HUVECs	[154]
	miR-205	OC	Promotes angiogenesis in ECs via PTEN-AKT signaling	[127]
	lncRNA-Ccat2	Glioma	Proliferation of ECs via upregulation of VEGF-A and TGFβ. Inhibition of apoptosis by targeting Bax and caspase-3	[155]
	lncRNA-Pouf3	Glioma	Pro-angiogenic gene expression in ECs	[155]
Lymphangiogenesis	miR-221-3p	CeC	Expansion of lymphatic vessels via downregulation of VASH	[156]
	LNMAT2	Bladder cancer	Growth of lymphatic vessels via upregulation of PROX1	[157]
Organo- tropism	miR-141-3p	PC	Bone metastasis via increased osteoblast activity	[15]
	miR-940	PC, BC	Bone metastasis via increased osteoblast activity	[158]
PMN	miR-122	BC	Suppression of glycolytic enzymes in non-tumor cells	[116]
	miR-1247-3p	HCC	CAF formation	[159]
	miR-451	CAFs in ESCC	Pro-tumor PMN formation	[160]
	miR-25-3p	CRC	Enhanced vascular permeability and angiogenesis in PMN via targeting KLF2 and KLF4	[161]

Abbreviations: BC: breast cancer; CCRCC: clear cell renal cell carcinoma; CeC: cervical cancer; CRC: colorectal cancer; ESCC: esophageal squamous cell carcinoma; GBM: glioblastoma; GC: gastric cancer; HCC: hepatocellular carcinoma; LC: lung cancer; NPC: nasopharyngeal carcinoma; NSCLC: non-small-cell lung cancer; OC: ovarian cancer; OSCC: oral squamous cell carcinoma; PC: prostate cancer; PDAC: pancreatic ductal adenocarcinoma; TAM: tumor-associated macrophage; CAF: cancer-associated fibroblast; PMN: pre-metastatic niche.