The role of vitamins and minerals in modulating the expression of microRNAs
Emma L Beckett, Zoe Yates, Martin Veysey, Konsta Duesing and Mark Lucock
Table S1: Summary of studies linking modulation of miRNA expression to nutritional status of vitamins and minerals
Nutritional status / miRNA / Direction of modulation / Target/Pathway / NotesHuman Cohort Studies
Serum/plasma
vitamin D / 532-3p(103) / ↓↑ / - / Positive correlation between expression and serum 25-hydroxyvitamin D levels
92b
93
138
196a*
320d
423-3p
484
573
589
601
574-5p(104) / ↓
↑ / 305 genes (299 up-regulated and 6 down-regulated)differentially expressed / miRNAs are differentially expressed between low (less than or equal to 25.5ng/ml) or high (greater than or equal to 31.7ng/ml)
Folate intake / 222(109) / ↓ / - / Inverse correlation between expression and intake
Zinc depletion / 10b
155
200b
296-5p,
373
92a
145
204 211(152) / ↓ / Parallel decrease in ability of blood cells to produce TNFα in response to inflammatory stimuli / miRNA levels increased again following repletion
Animal Model Studies
Methyl donor deficiency / let-7a
21
23
130
190
17-92
122(112) / ↑
↓ / - / Methyl donor deficient diet leads to Hepatocellular carcinoma after 54 weeks
Return to control diet at 36 weeks led to return to normal miRNA profiles and no induction of disease
34a
16a
181a
127(113) / ↓ / Increased levels of E2F3 and BCL6, proteins known to be regulated by miR-34a and miR-127 respectively / All are known tumour suppressor miRNAs
Choline and amino acid deficiency / 21
155
221
222(114) / ↑ / Correlated with significant reduction in the expression of hepatic phosphatase and tensin homolog (PTEN) and CCAAT/enhancer binding protein beta (C/EBPbeta), targets of miR-21 and miR-155, respectively / PTEN and C/EBPbeta are tumours suppressor genes
Retinoic acid treatment / 9
124a
125b(117, 120) / ↓ / Spinal development / Rat model of spina bifida
Vitamin C deficiency / let-7b
16
30a
126
143
322
721
let-7c(131) / ↑
↓ / Reduced capacity to oppose oxidative stress / Murine ovarian follicular cells in enzyme L-gulono-y-lactone oxidase deficient mice
Vitamin E deficiency / 122
125b(142) / ↓ / Correlated with reduced plasma cholesterol / Synthetic inhibition of miR-122 in mice led to the increase of expression of 108 genes related to lipid metabolism(143,144)
Cell Culture System Studies
Vitamin D treatment / 22(92) / ↑ / Correlates with reduced proliferation in colon cancer cell lines / Expression and reduction of proliferation occurred in a time, dose and VDR dependent manner
32(168) / ↑ / Suppressed expression of Bim pro-apoptotic factor / Induced features of normal monocytes in AML cells
181a(99) / ↓ / Led to the arrest of cell cycle progression in the G1 phase / Expression occurred in a dose and time dependent manner in Leukaemia cell lines (HL60 and U937)
26b
182
200b/c
let-7(100) / ↓ / Serum-starvation (low serum content media) increased miRNA expression, vitamin D treatment reverses this / Breast epithelial cell line (MCF12F)
Folate deficiency / let-7a
15a/b
16
29a/b
34a
130b
125a-5p
124
290-3p
302a(108) / ↑
↓ / Inhibited growth with a higher rate of apoptosis led to accumulation in G0/G1 phase of the cell cycle / Murine embryonic stem cells
222 (109) / ↑ / TK-6 human lymphoblast cell line
Retinoic acid treatment / 9
103(117) / ↑ / ID2, a transcription factor expressed in neural precursor cells, but also up-regulated during tumourigenesis in the neural system / Treatment leads to differentiation and inhibition of proliferation in neuroblastoma cell lines
152(118) / ↑ / DNMT1 / Neuroblastoma cell line (SK-N-BE)
29a(123)
142-3p / ↑ / Induced granulocytic differentiation / Leukaemia cell lines (HL-60, THP-1 and NB4)
let-7d/a-3
15a
16-1
107
223(125) / ↑ / Down-regulated Bcl-2 (apoptosis regulator) and Ras / NF-κB recruitment on the let-7 cluster
Vitamin C treatment / 146(130) / ↑ / Induction of cellular differentiation / Periodontal ligament cells (multi-potent population)
Selenium treatment / 34(149) / ↑ / Positive correlation with p53 expression / LNCaP human prostate cancer cell line
References
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