Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

Table 2

Summary of exosomal miRNAs with a potential biomarker role in CRC or whose expression is associated with CRC diagnosis and progression. The main source of exosomes referred in the literature is indicated. Exosome isolation techniques employed in the diverse references 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	Validation	Associated effect	References
mir-221	Cell supernatant (HT-15, SW480, WiDR)	UC	WB : CD81	Biomarker for tumor size, TNM stage, Dukes stage, lymph node metastasis, recurrence	[99, 135]
mir-215	(i) Cell supernatant; (a) HT-15, SW480, WiDR; (b) CAFs, NOFs	(i) UC; (ii) UC	(i) WB : CD81/NTA + TEM + WB; (ii) NTA + TEM + WB	Upregulation in CAF exosomes	[99, 103]
mir-23a	(i) Serum; (ii) Cell supernatant (SW48, SW480, SW620, HCT116, HT29, RKO)	(i) UC; (ii) UC	(i) TEM/WB; (ii) TEM/WB	Diagnosis biomarker associated with liver metastasis recurrence	[9, 11]
mir-320a, -4476	(i) Tissue; (ii) Serum	UC	TEM	Associated with liver metastasis recurrence	[9]
mir-125a	Plasma	ExoQuick	SEM/none	Early tumor stage biomarker	[27, 136]
mir-320c	Plasma	ExoQuick	SEM	Higher levels in CRC patients	[136]
mir-328	Plasma (mesenteric vs. peripheral)	UC	TEM + WB : Tsg101	Liver metastasis biomarker (better performing in mesenteric vein)	[105]
mir-4472-3p	Serum	ExoQuick	TEM + WB	Diagnosis and tumor recurrence biomarker	[137]
mir-6803-5p	Serum	Total exosome isolation kit	None	Diagnosis and prognostic biomarker, associated with stage and lymph node metastasis	[138]
mir-4644	Meta-analysis	—	—	GI cancer diagnosis biomarker	[102]
mir-7641	Cell supernatant (HT-15, SW480, WiDR)	UC + OptiPrep	TEM + WB : Alix, Tsg101	Diagnosis biomarker	[107]
mir-638	Serum	Total exosome isolation kit	None	Biomarker for TNM stages III-IV and liver metastasis	[77, 78]
mir-548c	(i) Serum; (ii) Plasma (mesenteric vs peripheral)	(i) Total exosome isolation kit; (ii) UC	(i) None; (ii) TEM + WB : Tsg101	Diagnosis and prognostic biomarker, associated with faster relapse	[78, 105, 139]
mir-let-7a, -1229, -150, -223	(i) Cell supernatant (HCT116, HT29, RKO, SW48, SW480); (ii) Serum	UC	WB	Potential diagnosis biomarkers	[11]

GI cancers: gastrointestinal cancers; OptiPrep: commercial density gradient medium; TEM/SEM: electron microscopy (transmission/scanning); UC: ultracentrifugation (may include differential centrifugation steps and eventual additional filtering); WB: western blot. Total exosome isolation kit (Invitrogen), ExoQuick (System Biosciences), and qEV SEC (Izon): commercial exosome purification solution or kits.