Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

Table 1

Summary of exosomal miRNA with known functions in CRC. The main source of exosomes in the publications is indicated. Exosomes isolation techniques employed in the literature are indicated with their respective exosome enrichment validation procedures. Without any other mentions, plasma and serum are to be considered from human origin.

miRNA	Exosome source	Isolation technique	Exosome validation technique	Associated function	References
miR-21	(i) Cell supernatant; (a) HCT-15, SW480, WiDR; (b) CAFs, NOFs; (c) Macrophages; (ii) Serum; (iii) Plasma (whole/mesenteric vs peripheral)	(i) UC; (ii) UC/ExoQuick; (iii) UC	(i) (a) WB : CsD81, (b) NTA/TEM/WB, (c) TEM/WB; (ii) WB : CD81/none; (iii) TEM/TEM + WB : Tsg101	Diagnosis biomarker, migration, invasion, liver metastasis, chemoresistance	[11, 99–105]
miR-155	(i) Plasma (whole/mesenteric vs peripheral); (ii) Cell supernatant (macrophages)	UC	(i) TEM/TEM + WB : Tsg101; (ii) NTA + TEM + WB	Migration, invasion	[104, 105]
miR-17∼92 and 25∼106b clusters	(i) Cell supernatant (SW480, SW620); (ii) Serum	(i) UC + OptiPrep; (ii) qEV SEC/ExoQuick/UC	(i) TEM + WB; (ii) EM + WB/-/TEM/TEM + WB	Diagnosis biomarker	[9, 23, 101, 106, 107]
miR-25-3p	(i) Cell supernatant (SW480, HCT116); (ii) Serum	UC	TEM + WB	Migration, angiogenesis, vascular permeability, pre-metastatic niches	[23]
miR-200 family	(i) Cell supernatant; (a) SW640, SW480; (b) CCL27 (spheroid cultures); (ii) Plasma (mesenteric vs peripheral)	(i) (a) UC, (b) ExoQuick-TC; (ii) UC	(i) (a) TEM, (b) None; (ii) TEM, WB : Tsg101	EMT reversion marker, preventing permeation, associated with lower survival in exosomes	[98, 108–110]
miR-200b	Cell supernatant (SW480, HCT116)	UC	TEM + NTA	Proliferative activity	[98]
miR-1246	(i) Cell supernatant: (HCT116, HT29, SW480, Colo201, WiDR); (ii) Serum; (iii) Plasma	UC	(i) WB : CD81/NTA/TEM; (ii) WB : CD81; (iii) NTA + TEM + WB	Diagnosis biomarker, proliferation, migration, angiogenesis, pre-metastatic niches induction, TAM reprogramming	[11, 23, 102, 111]
mir-96 and mir-149	(i) Tissue; (ii) Plasma	ExoCapTM + SG + FACS	TEM + WB : CD63	Tumor suppressor	[112, 113]
mir-486-5p	Plasma	Total exosome isolation kit	None	Tumor suppressor	[78, 114]
mir-6869-5p	Serum	Total exosome isolation kit	None	Prognostic biomarker, tumor suppressor	[78, 115]
mir-8073	Cell supernatant-HCT116	UC	None	Tumor suppressor	[116]
mir-193a	(i) Modified CT26 cells xenograft; (ii) Serum	(i) UC + SG, pulldown; (ii) exoEasy	NTA	Tumor suppressor	[92]
mir-10b	(i) Tissue; (ii) Cell supernatant (HCT116)	UC + ExoQuick + exosomes precipitation solution	TEM-IG + WB	Oncogenic, CAF transformation	[117]
mir-142-3p	Cell supernatant (HCT-116, HT-29, SW480, MSCs)	UC	NTA + TEM-IG + WB	Induces stemness	[118]
mir-196b-5p	Serum	—	—	Induces stemness prognostic biomarker	[119]
mir-210	Cell supernatant (HCT-8)	Exosome precipitation solution	TEM	Induces EMT transition	[19]

EMT: epithelial-mesenchymal transition; FACS: fluorescence-activated cell sorting; MSCs: mesenchymal stem cells; OptiPrep: commercial density gradient medium; SG: sucrose gradient; TAM: tumor-associated macrophages; TEM/TEM-IG: electron microscopy (transmission/transmission coupled with immunogold labelling); UC: ultracentrifugation (may include differential centrifugation steps and eventual additional filtering); WB: western blot. Total exosome isolation kit (Invitrogen), ExoQuick (System Biosciences), exoEasy or exoRNeasy (Qiagen), qEV SEC (Izon), ExoCapTM (JSR), and exosome precipitation solution (Macherey-Nagel): commercial exosome purification solution or kits.