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.