MicroRNA biomarkers predicting risk, initiation and progression of colorectal cancer

Table 2 Summary of dietary regulation of microRNAs, potentially relevant to colorectal cancer

MicroRNA	Study population	Diet or nutrient	Analysis method	Findings	Specimen type	Ref.
miR-16 miR-21 miR-34a miR-92a miR-106a miR-146 miR-222	Italian-based 8 vegans 8 vegetarians 8 omnivores	Meat, processed meat, fish, cheese	Food frequency and lifestyle questionnaire	miR-92a was significantly decreased by meat and dairy products, and associated with low body mass index. Weaker associations found between miR-21 levels and vegetable intake	Plasma and stool	Tarallo et al[38]
Let-7d miR-15b miR-107 miR-191 miR-324-5	Sprague-Dawley rats, treated with saline or the carcinogen, azoxymethane	Corn oil vs fish oil in the diet	Effects of diets on the expression of 368 miRNAs in the colonic mucosa	The five identified miRNAs were the most strongly affected by diet X carcinogen actions. The fish fed animals showed the smallest number of differentially expressed miRNAs - interpreted as due to a reduction in inflammation	Colonic mucosa	Davidson et al[39]
miR-1903 miR-467c miR-368 miR-927c	Female athymic nude mice, injected with HT-29 colon cancer cells	Corn oil vs ground walnuts in the diet	Effects of the diets on the expression of four microRNAs in the colon tumours	The first three of these microRNAs were down-regulated and the latter up-regulated in expression. These data were related to significant increases in α-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid in the walnut fed mice	Colorectal tumour tissue	Tsoukas et al[40]
miR-155	Young subjects (22 + 2 yr), smokers and non-smokers	High dose vitamin C daily for 8 wk	Expression level of miR-155 in HDL3	miR-155 reduced in HDL fraction by 49% in non-smokers and 75% in smokers after 8 wk supplementation. This effect was related to a reduction in reactive oxygen species	Serum lipoprotein levels	Kim et al[43]
miR-98 miR-92a miR-30e miR-140-5p miR-138	7 different prostate cell models including malignant and non-malignant	30 min treatment with 1a,25(OH)2D3	MiRNA microarray analyses	111 miRNAs showed changed expression levels, but only 5 were seen affected in more than one cell line and only 3 were changed in the same direction	Total mRNA and miRNA from each cell line.	Singh et al[44]
miR-22 miR-29ab miR-134 miR-1207-5p miR-371-5p miR-17 miR-20a	LNCaP human prostate cancer cells	48 h treatment with 100 nmol/L 1,25(OH)2D3 compared with non-treated control, cells	Agilent human microRNA v3 microarrays to measure microRNA expression	Four hundred and twenty genes were up-regulated and 413 genes down-regulated in the 1,25(OH)2D3-treated cells. The most strongly affected are those identified in column 1 (the last two of these miRNAs is downregulated)	Integrative network-based analysis using a publicly available data set	Kutmon et al[45]
miR-155	RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS)	24 h in the presence of EtOH or 20 nmol/L 1,25(OH)2D3	miRNA profiling by microarrays	Several miRNAs were induced by LPS and suppressed by 1,25(OH)2D3, of which miR-155 was on the top of the list, suppressing about 50% of the LPS induction	Total mRNA and miRNA from each cell line	Li et al[46]
miR-22	SW480-ADH and HCT116 colon cancer cells	10-7 mol/L 1,25(OH)2D3 for 24, 48 or 96 h	miRNA profiling by microarrays	Although there were 12 microRNAs that showed differential expression with and without vitamin D, miR-22 showed the most consistent differences	Total miRNA from each cell line	Alvarez-Díaz et al[48]
Let-7f Let-7a miR-151-5p miR-22 miR-221 miR-28-5p miR-552-3p miR-766 miR-99b	Males, generally in good health, with no diabetes or other concomitant diseases	High dose vitamin D3 (20000-40000 IU per week)	Quantitative real-time PCR	In 10 pilot subjects, 136 miRNAs were changed in expression in one or more plasma samples drawn at baseline and after 12 mo of vitamin D supplementation. The twelve miRNAs that showed the greatest change in expression in the pilots were further measured in RNA from baseline and 12 mo plasma samples in 40 subjects given vitamin D and 37 subjects given placebo	Plasma	Jorde et al[47]
miR-122a miR-125b	Fischer 344 rats	0, 12 or 24 mg/kg	Quantitative real-time PCR	Vitamin E sufficiency resulted in increased concentrations of miRNA-122a and miRNA-125b	Liver tissue	Gaedicke et al[49]
miR-625 miR-492 miR-373 miR-22, miR-532-5p miR-106b miR-30b miR-185 miR-203 miR1308 miR-28-5p miR-10b	CaCO2 human colon cancer cells	Selenium-deficient or sufficient medium	Microarray validated with quantitative real-time PCR	Selenium deficiency resulted in altered expression of 12 genes	Total miRNA from combined cells of each treatment	Maciel-Dominguez et al[50]
miR-21	U251 human glioblastoma cells	10, 50 or 100 umol/L Resveratrol for 72 h	Quantitative real-time PCR	Resveratrol inhibited miR-21 expression which in turn suppressed NF-κB activity. However, over-expression of miR-21 could reverse the effect of resveratrol on NF-κB activity and apoptosis	Cell extracts	Li et al[54]
miR-21	Estrogen-dependent MCF-7 and estrogen receptor-negative p53 mutant MDA-MB-468 human breast cancer cells	0, 30 or 60 umol/L	Quantitative real-time PCR	Cells were studied either in tissue culture or as a xenograft in BALB/C female athymic mice miR-21 was up-regulated in DIM-treated MCF-7 cells, but not in the ER negative, p53 mutant MDA-MB-468 cells	Cell extracts	Jin[55]
miR-30b miR-1224-3p miR-197 miR-523-3	HepG2 human hepatocarcinoma cells	3-3’-Diindoyl-methane for 24-96 h 50 mg/L of epigallocatechin gallate (EGCG), 100 mg/L of grape seed extract (GSPE) or 100 mg/L of cocoa proanthocyanidin extract (CPE)	Microarray analysis validated by quantitative real-time PCR	MiR-30b was downregulated by all three treatments, while treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p	Cell extracts	Arola-Arnal et al[57]
miR-210 (plus 13 other miRNAs upregulated and 7 down-regulated)	Tobacco carcinogen-induced lung cancer in A/J mice	Purified mouse chow containing 0.4% EGCG	Microarray analysis validated by quantitative real-time PCR	MiR-210 had been previously found upregulated by EGCG in in vitro experiments, but this ranked behind the 13 most strongly upregulated miRNAs (miR-2137, miR-449a, miR-144, miR-486, miR-3107, miR-193, miR-5130, miR-2861, miR-511-3p, miR-763, miR-3473, miR-211, miR-210) or seven most down regulated in this in vivo study	Tumour tissue, all tumours from a single mouse combined to a single sample	Zhou et al[58]