Table 4.
miRNAs and their targets involved in CRC chemoresistance.
| miRNA | Key Targets | Pathways Affected | Role in CRC | References |
|---|---|---|---|---|
| miR-145-5p | BIRC5, Fli-1 | Apoptosis, Drug resistance | Sensitizes CRC cells to 5-FU by repression of Fli-1; potential target of BIRC5; downregulated in CRC and associated with oxaliplatin resistance | [389,401,402] |
| miR-150-5p | BIRC5 | Apoptosis | Regulates apoptosis by targeting BIRC5; downregulation linked to CRC progression | [389] |
| miR-195-5p | BIRC5, BCL2, BCL2L2, YAP | Apoptosis, Drug resistance, Hippo-YAP | Downregulated in CRC; sensitizes cells to oxaliplatin and 5-FU by targeting BCL2 and BCL2L2; promotes apoptosis; overexpression inhibits tumorigenicity; associated with 5-FU resistance in HT29/DOX and LOVO/DOX cells | [123,124,389,394] |
| miR-650 | BIRC5 | Apoptosis | Potential regulator of apoptosis by targeting BIRC5 | [389] |
| miR-92a-3p | CSF2RB | Apoptosis | Targets CSF2RB; involved in apoptosis regulation | [389] |
| miR-20b-5p | CTSS, ADAM9, EGFR | Apoptosis, EMT | Downregulated in 5-FU-resistant CRC cells; resensitizes CRC cells to 5-FU by inducing apoptosis and repressing ADAM9 and EGFR | [389,410] |
| miR-501-3p | CTSS | Apoptosis | Potential regulator of CTSS and apoptosis in CRC | [389] |
| miR-497-5p | KSR1, BCL2, IGF1-R | Apoptosis, Drug resistance, EMT | Downregulated in CRC; sensitizes cells to oxaliplatin and 5-FU; promotes apoptosis by targeting IGF1-R and BCL2; inhibits EMT and cell proliferation; enhances chemosensitivity | [117,120,394,395] |
| miR-125-5p | MSI1, BCL2, Mcl-1, CXCR4 | Apoptosis, EMT, Autophagy | Tumor suppressor in CRC; downregulation leads to resistance to FOLFOX; targets BCL2, BCL2L12, and Mcl-1; modulates CXCR4 and APC signaling; also involved in drug resistance and autophagy | [396,[398], [399], [400]] |
| miR-34a | SIRT1, E2F3, OAZ2 | Apoptosis, Drug resistance, EMT | Downregulated in 5-FU-resistant CRC cells; targets SIRT1, E2F3, and OAZ2; sensitizes multidrug-resistant CRC cells to 5-FU and oxaliplatin treatment | [[405], [406], [407]] |
| miR-19b-3p | SMAD4 | Apoptosis, Drug resistance | Mediates oxaliplatin resistance by targeting SMAD4; overexpressed in patients with poor prognosis; inhibition of its exosomal secretion enhances oxaliplatin sensitivity | [408,409] |
| miR-17-5p | PTEN | Apoptosis, Drug resistance | Upregulated in chemoresistant CRC; promotes invasiveness and multidrug resistance (MDR) by targeting PTEN | [180] |
| miR-143 | HK II | Glycolysis, Apoptosis, Drug resistance | Downregulated in CRC and 5-FU-resistant CRC cells; inhibits glycolysis by targeting HK II, resensitizes cells to 5-FU; inhibits proliferation and migration | [86,100,403] |
| miR-206 | Bcl-2 | Apoptosis, Drug resistance | Downregulated in CRC; promotes drug resistance by targeting Bcl-2 | [411] |
| miR-133b | DOT1L | Stemness, Chemoresistance | Tumor suppressor miRNA; downregulated in CRC; reduces CRC stemness and abrogates chemoresistance to 5-FU and oxaliplatin by targeting DOT1L | [412] |
| miR-203 | ATM, HOTAIR | DNA damage response, Drug resistance | Upregulated in oxaliplatin-resistant CRC lines; downregulation sensitizes cells to oxaliplatin by targeting ATM | [375,413] |
| miR-192/215 | TYMS | S-phase, Drug resistance | Downregulated in CRC; modulates TYMS expression, which affects the efficacy of fluoropyrimidine-based chemotherapy | [414,415] |
| miR-200 family | - | EMT, Drug resistance | Associated with better prognosis in CRC patients treated with fluoropyrimidine-based chemotherapy; high levels correlate with longer survival | [416] |