Table 1.

Summary of the most frequently dysregulated miRNA clusters in CRC.

Cluster	Dysregulation	Function/Role	Related Information	miRNA	Target	Reference
miR-143/145	Downregulated	Tumor suppressors	Frequently downregulated in CRC due to hypermethylation of their CpG islands.	miR-145	IRS1	[84]
					MUC1	[85]
					BRAF and CD44	[86]
					IGF1R	[87]
					KLF5	[86]
					MDM2	[88]
					MYC	[89]
					NRAS	[90]
					FSCN1	[91]
					CDCA3	[92]
					MAPK1	[93]
					SIP1	[94]
					catenin δ-1	[95]
					YES and STAT1	[96]
					PAK4	[97]
					ERG	[98]
					SOX2	[99]
				miR-143	BRAF and CD44	[86]
					MDM2	[88]
					MYO6	[100]
					KRAS	[101]
					MAPK7	[102]
					DNMT3A	[103]
					HKII	[104]
					MACC1	[105]
					BCL2	[100]
miR-1-2/133a-1, miR-1-1/133a-2, miR-206/133b	Downregulated	Tumor suppressors	myo-miRNAs, muscle-specific miRNAs generally down-regulated in CRC cell lines and tissue samples.	miR-133a	AFTPH	[106]
					FSCN1	[107]
					LASP1	[108]
					RFFL	[109]
				miR-133b	PTBP1	[110]
					MET	[111]
					CXCR4	[112]
				miR-206	NOTCH3	[113]
					MET	[114]
				miR-1	PTBP1	[110]
					NOTCH3	[115]
					SMAD3	[116]
miR-497/195	Downregulated	Tumor suppressors	Expression of miR-497-5p and miR-195-5p is down-regulated in CRC. Increased expression of miR-497-5p or miR-195-5p is associated with decreased cell proliferation, migration and EMT.	miR-497	IGF1-R	[117]
					FRA1	[118]
					IRS1	[119]
					KSR1	[120]
				miR-195	CDK8	[121]
					YAP1	[122]
					BCL2	[123]
					BCL2L2	[124]
					γ-catenin	[125]
					CCNE1	[126]
					AXIN2	[127]
miR-15a/16–1,miR-15b/16–2	Downregulated	Tumor suppressors	Although more frequently miR-15/16 in CRC is detected downregulated, there are also studies documenting up-regulation of miR-15/16 expression. Similarly, better survival is generally correlated with high expression of miR-15/16; however, an association of worse survival with high expression of miR-15/16 has also been documented.	miR-15a	AP4	[128]
					GPX4	[129]
					SIRT4	[130]
					KDM4B	[131]
				miR-15b	DCLK1	[132]
					NF-κB1 and IKK-α	[133]
					ACOX1	[134]
				miR-16	AP4	[128]
					BIRC5	[135]
					HMGA2	[136]
					ALDH1A3	[137]
					COX2	[138]
					ITGA2	[139]
miR-192/194–2 and miR-215/194–1	Downregulated	Tumor suppressors	Frequently downregulated in CRC, the reported functions of miR-192/194-2 and miR-215/194-1 clusters indicate their tumour-suppressive roles as cell cycle arrest and inhibition of cell adhesion are often observed after their overexpression.	miR-192	CAV1	[140]
					EIF5A2	[141]
				miR-194	VAPA	[142]
					KLK10	[143]
					MAP4K4	[144]
					THBS1	[145]
					PDK1, AKT2 and XIAP	[146]
					SSH2	[147]
					SOX5	[148]
					SIRT1	[149]
				miR-215	EREG and HOXB9	[150]
					Atg14	[151]
					CDX1	[152]
miR-183/96/182	Upregulated	Oncogenes	Frequently downregulated in CRC, miR-183/96/182 cluster promote migration, invasion and metastasis.	miR-183	ATG5	[153]
					FOXO1	[154]
					PFN2	[155]
					DNAJB4	[156]
					RCN2	[157]
				miR-96	TPM1	[158]
					CPA6	[159]
					AMPKα2	[160]
					TP53INP1, FOXO1, FOXO3a	[161]
				miR-182	NAMPT	[162]
					CFL1	[163]
					TIAM1	[164]
					DAB2IP	[165]
					SATB2	[166]
					ST6GALNAC2	[167]
					FoxF2	[168]
					TSP-1	[169]
miR-17/92a	Upregulated	Oncogenes	miRNAs of miR-17/92a cluster can act as oncogenes and promote proliferation, angiogenesis and inhibit differentiation and apoptosis.	miR-17	HSPB2	[170]
					MFN2	[171]
					BLNK	[172]
					RUNX3	[173]
					PLCD1	[174]
					CADM2	[175]
					VEGFA	[176]
					P130	[177]
					VIM	[178]
					SPOP	[179]
					PTEN	[180]
					RND3	[181]
					hCNT1	[182]
				miR-18a	ING4	[183]
					BTG3	[184]
					PIAS3	[185]
					TBPL1	[186]
				miR-19a	PTEN	[187]
					IREB2	[188]
					CLCA4	[189]
					THBS1	[190]
					KRAS	[191]
					FOXF2	[192]
					NPEPL1	[193]
				miR-19b	FBXW7	[194]
					PPP2R5E	[195]
					ACSL1, ACSL4, and SCD	[196]
				miR-20a	ATG5 and FIP200	[197]
					CXCL8	[198]
					PDCD4	[199]
					MICA	[200]
					FOXJ2	[201]
					PTEN	[202]
					SMAD4	[203]
				miR-92a	DKK3	[204]
					SOCS3	[205]
					NF2	[206]
					KLF4	[207]
miR-200c/141	Upregulated	Biomarkers	miRNA members of the miR-200c/141 cluster are found to be frequently upregulated in CRC at both tissue and circulating levels.	miR-200c	VLDLR	[208]
					KIF14	[209]
					JNK2	[210]
				miR-141	SIP1	[211]
					EGFR	[212]
					ZEB1 and ZEB2	[213]
					MAP4K4	[214]
					DLC1	[215]
miR-203a/203b	Upregulated	Biomarkers	miR-203a/203b are generally overexpressed in CRC and are associated with poor prognosis.	miR-203a	PTEN	[216]
					RNF6	[217]
					PDE4D	[218]
					THBS2	[219]
					CREB1	[220]
				miR-203b	BCL2L1	[221]
miR-222/221	Upregulated	Circulating biomarkers	Both members of the miR-222/221 cluster are positively correlated with disease recurrence and are frequently detected upregulated in in the circulation of patients with CRC.	miR-222	SPINT1	[222]
					CD4	[223]
					ADAM-17	[224]
					MIA3	[225]
					ATF3	[226]
					BRG1	[227]
					MST3	[228]
				miR-221	SPINT1	[222]
					CD4	[223]
					TP53INP1	[229]
					CDKN1C/p57	[230]
					SOCS3	[231]
					RECK	[232]
23a/27a/24–2	conflicting data	conflicting data	Members of miR-23a/27a/24-2 cluster has been proposed to control the cell cycle, cell proliferation, cell death and cell differentiation.	miR-23a	SEMA6D	[233]
					APAF1	[234]
				miR-27a	c-Met	[235]
					BTG2	[236]
					RMST	[237]
				miR-24	NRP1	[238]
miR-29b-1/29a	Upregulated	Biomarkers	miR-29b-1/29a seems to have a biomarker value for risk, recurrence, metastasis and survival outcome of CRC.	miR-29b-1	SMAD3	[239]
				miR-29a	RPS15A	[240]
					TNFAIP3	[241]
					KLF4	[242]
miR-301b/130b	Upregulated	Oncogenes	Members of the miR-301b/130b cluster act as oncogenes by promoting cell growth and migration and may serve as biomarkers for the diagnosis of CRC.	miR-301b	HOXB1	[243]
				miR-130b	CHD9	[244]
					integrin α5	[245]