Table 1.
Summary of the miRNA and their functions in CRC.
| miRNA | Dysregulation in Function colorectal cancer | KRAS as a target gene (www.targetscan.org) | References | |
|---|---|---|---|---|
| Let-7 | Downregulated | Overexpression of Let-7a-1 in DLD1 and SW480: Inhibits growth and cell proliferation Reduces KRAS and C-myc protein àdecrease the radiosensitization of cells during therapy Overexpression of Let-7d in HCT15: Reduces KRAS mRNA and protein expression in smooth muscle cell Reduces cell growth Induced G1 cell cycle Increase in microsatellite stability (MSS) | KRAS is a target of: Let-7a-3p, Let-7a-2-3p Let-7b-3p Let-7c-3p Let-7f-1-3p Let-7g-3p | 11,26,27,29 |
| miR-18a-3p | Downregulated | Inhibition in HT29, A431 and WRL-68 cells: Increases KRAS expression Promotes cell proliferation Promotes Anchorage-independent growth in soft agar | KRAS is a target of miR-18a-3p, but not miR-18-5p. | 38 |
| miR-29b-3p | Downregulated | Overexpression in SW480 cells: Reduces ki-67 level which showed low cell proliferation, Stimulate apoptosis Arrest cells at G1/S Cell Cycle Overexpression of MIRTX (complementary strand of miR-29b-1-5p) in DLD1 and SW480: Anti-tumor effect on KRAS mutant CRC Inhibits cell proliferation Induces apoptosis - by regulating antiapoptotic and proapoptotic proteins - suppresses NF-kB pathway | KRAS is a target of miR-29b-1-5p, but not miR-29b-2-5p | 41 |
| miR-30b | Downregulated | Overexpression in SW620 and HCT116: Reduces cell proliferation, Reduced tumor growth in mouse xenograft, Increases G1 cell arrest Induces apoptosis | KRAS is a target of both miR-30-5p and miR-30-3p, but not miR-30b-3p | 24 |
| miR-31-3p | Upregulated | miR-31 inhibits RASA1, which enhances GTPase for RAS - Indirectly targets 3’ UTR of KRAS Inhibition of RASA1: Increases phosphorylation of ERK1/2 Promotes cell proliferation Suppresses apoptosis Deregulate cell cycle | KRAS is not listed as a target of miR-31-3p in TargetScan database. | 49 |
| miR-96 | Downregulated | Overexpression in HCT-116 Reduced cell growth Reduced colonies in soft agar Reduced in proliferation marker cyclin D1 Increase in cell cycle inhibitor p27 gene When treated with Resveratrol (in vivo) Reduced KRAS expression Reduced tumor progression and growth Delayed onset of tumor | KRAS is a target of miR-96-5p, but not miR-96-3p | 9,53 |
| miR-126 | Downregulated | Overexpression in HCT116, LoVo, SW403, SW116 and SW620: Reduces cell viability, but not miR-126-3p Increase G1 compartment Inhibit colony formation Increase apoptosis, Decreased tumor growth in mouse xenografts *Lower miR-126 expression is exclusively found in KRAS mutant only | miR-126-5p targets KRAS, | 55-57 |
| miR-143 | Downregulated | Overexpression in LoVo, SW480 and DLD-1 cells: Reduces KRAS expression by inhibiting KRAS mRNA in translational level Inhibits ERK1/2 phosphorylation that results in the Inhibition of tumor cell growth Inhibition in LoVo and SW480 cells: Increased in cell viability and cell proliferation | miR-143-3p targets KRAS, but miR-143-5p does not | 19,59 |
| miR-155 | Upregulated | Overexpression in HT-29 cells: Promotes proliferation, invasion and metastasis | miR-155-5p targets KRAS, but | 16 |
| (Downregulated) | *Transfection of miR-155 reduces KRAS protein level | miR-155-3p does not | 67 | |
| miR-193a-3p | Downregulated | Overexpression in SW480 and SW48 Reduced amount of K-ras proteins Reduces cell proliferation and cell migration by inhibiting EMT markers Involved in cell cycle event - reduction of cells in the G0/G1 phase and increase in G2-M phase Showed apoptotic cell structure by either shrinkage or fragmentation (under fluorescence) | miR-193-3p is a target for KRAS, but not miR-193a-5p | 25,68 |
| miR-200c | Upregulated | Overexpression in RKO and SW620 cells Increases cell proliferation Reduced cell invasion and migration KRAS level is higher in DLD-1 cells and HCT116 cells when compared with their respective knockdown cells. miR-200c is a modulator of EMT by inhibiting ZEB1 and ZEB2 in these cells. *High miR-200c is exclusively found in KRAS mutated CRC | miR-200bc-3p is a target for KRAS, but not miR-200c-5p | 17,71-75 |
| miR-217 | Downregulated | Overexpression in RKO and SW480 cells Inhibit tumor growth Reduces cell proliferation Enhances apoptosis by decreasing Bcl-xl and Bcl-2 miR-217 targets 3’UTR of MAPK1 and KRAS | miR-217 is a target for KRAS | 78,87 |
| miR-384 | Downregulated | Overexpression in SW480 and HCT116 cells Reduces cell viability Inhibits cell migration and invasion Reduction of metastatic nodule in liver (in vivo) Inhibition in LoVo and SW620 cells Stimulates cell viability Increase cell migration and invasion | miR-384 is a target for KRAS | 82 |
| miR-543 | Downregulated | Target gene: KRAS, MTA1 and HMGA2 Overexpression in SW620 and LoVo cells Inhibits KRAS mRNA Reduces expression levels of p-MEK and p-ERK Represses cell proliferation and metastasis Inhibit tumor growth, in vivo *Directly targets KRAS, MTA1 and HMGA2 | miR-543 is a target for KRAS | 84,85 |
| miR-4689 | Downregulated | Overexpression in DLD-1 cells Induces proapoptotic genes, BAX, BAD, BAK and Cyt C Suppresses antiapoptotic genes; BCL2 and BCLXL In vivo, miR-4689 inhibit tumor growth in mouse xenograft *Direct targets: KRAS and AKT1 at mRNA and protein level *Exclusively targets KRASG12V CRC | miR-4689 is not listed as a target for KRAS in TargetScan | 86 |