Plasma profile of microRNA after supplementation with high doses of vitamin D3 for 12 months

BMC Research Notes

Dag H Coucheron¹  Ragnar Martin Joakimsen²  Johan Svartberg²  Rolf Jorde² 

[1] RNA and Transcriptomics Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway;Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway and Division of Internal Medicine, University Hospital of North Norway, 9038, Tromsø, Norway

关键词: Vitamin D;    Randomized clinical trial;    microRNA;   

Others  :  1166408
DOI  :  10.1186/1756-0500-5-245

 received in 2012-02-10, accepted in 2012-05-17,  发布年份 2012

【 摘 要 】

Background

Recently a large number of short non-coding-RNAs (microRNAs, (miRNA)) have been identified. These miRNAs act as post-transcriptional regulators where they generally have an inhibitory function. miRNAs are present in all human cells, and they are also detected in serum or plasma. The miRNAs have a broad range of actions, and their biogenesis must therefore be under tight control. One putative regulator of miRNA biogenesis or miRNA level could be vitamin D, an ancient hormone with effects on cell growth and differentiation, apoptosis and the immune system. In our study miRNA were reversed transcribed in total RNA isolated from plasma and analyzed by quantitative real-time PCR (qPCR) using the miRCURY LNA Universal RT microRNA PCR system (Exiqon). In 10 pilot subjects 136 miRNAs were detected in one or more plasma samples drawn at baseline and after 12 months of vitamin D supplementation. The twelve miRNAs that showed the greatest change in expression in these pilots were further analyzed by RT-qPCR of RNA from baseline and 12 months plasma samples in 40 subjects given high dose vitamin D₃ (20.000 – 40.000 IU per week) and 37 subjects given placebo.

Results

At baseline there was a significant and positive correlation between serum 25-hydroxyvitamin D and miR-532-3p expression (r = 0.24, P = 0.04). The change in expression of miR-221 from baseline to 12 months (ddCp value) was also significantly different between the vitamin D and placebo group (P =0.04), mainly due to a change in the placebo group.

Conclusions

We have not been able to demonstrate a consistent effect of vitamin D supplementation on the expression profile of miRNA in plasma. However, further studies are needed as this approach might potentially throw light on unknown aspects of vitamin D physiology.

【 授权许可】

   
2012 Jorde et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR: RNA maps reveals new RNA classes and a possible function for persvasive transcription. Science 2007, 316:1484-1488.
• [2]Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS: Non-coding RNAs: regulators of disease. J Pathol 2010, 220:126-139.
• [3]Lee RC, Feinbaum RL, Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75:843-854.
• [4]Kozomara A, Griffiths-Jones S: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011, 39:D152-D157.
• [5]Williams AE: Functional aspects of animal microRNAs. Cell Mol Life Sci 2008, 65:545-562.
• [6]Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R: MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA 2008, 105:1608-1613.
• [7]Filipowicz W, Bhattacharyya SN, Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008, 9:102-114.
• [8]Friedman RC, Farh KK, Burge CB, Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009, 19:92-105.
• [9]Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse. Curr Biol 2002, 12:735-739.
• [10]Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM: Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 2003, 113:25-36.
• [11]Cuellar T, McManus MT: MicroRNAs and endocrine biology. J Endocrinol 2005, 187:327-332.
• [12]Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M: A pancreatic islet-specific microRNA regulates insulin secretion. Nature 2004, 432:226-230.
• [13]Kocerha J, Kauppinen S, Wahlestedt C: MicroRNAs in CNS disorders. Neuromolecular Med 2009, 11:162-172.
• [14]Barringhaus KG, Zamore PD: MicroRNAs: regulating a change of heart. Circulation 2009, 119:2217-2224.
• [15]Nathans R, Chu CY, Serquina AK, Lu CC, Cao H, Rana TM: Cellular microRNA and P bodies modulate host-HIV-1 interactions. Mol Cell 2009, 34:696-709.
• [16]Medina PP, Slack FJ: MicroRNAs and cancer: an overview. Cell Cycle 2008, 7:2485-2492.
• [17]Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008, 18:997-1006.
• [18]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008, 105:10513-10518.
• [19]Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL: Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008, 141:672-675.
• [20]Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D: Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 2008, 58:1001-1009.
• [21]Carthew RW, Sontheimer EJ: Origins and Mechanisms of miRNAs and siRNAs. Cell 2009, 136:642-655.
• [22]DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004, 80(6 Suppl):1689S-1696S.
• [23]Bouillon R, Okamura WH, Norman AW: Structure-function relationships in the vitamin D endocrine system. Endocr Rev 1995, 16:200-257.
• [24]Autier P, Gandini S: Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007, 167:1730-1737.
• [25]Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF: The role of vitamin D in cancer prevention. Am J Public Health 2006, 96:252-261.
• [26]Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS: Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008, 117:503-511.
• [27]Cantorna MT, Zhu Y, Froicu M, Wittke A: Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004, 80:1717S-1720S.
• [28]Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A: Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diab Care 2007, 30:2569-2570.
• [29]Nagpal S, Na S, Rathnachalam R: Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005, 26:662-687.
• [30]Holmén J, Jansson A, Larsson D: A kinetic overview of the receptors involved in 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 signaling: a systems biology approach. Crit Rev Eukaryot Gene Expr 2009, 19:181-196.
• [31]Wang WL, Chatterjee N, Chittur SV, Welsh J, Tenniswood MP: Effects of 1α,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer 2011, 10:58. BioMed Central Full Text
• [32]Enquobahrie DA, Williams MA, Qiu C, Siscovick DS, Sorensen TK: Global maternal early pregnancy peripheral blood mRNA and miRNA expression profiles according to plasma 25-hydroxyvitamin D concentrations. J Matern Fetal Neonatal Med 2011, 24:1002-1012.
• [33]Peng X, Vaishnav A, Murillo G, Alimirah F, Torres KE, Mehta RG: Protection against cellular stress by 25-hydroxyvitamin D3 in breast epithelial cells. J Cell Biochem 2010, 110:1324-1333.
• [34]McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A: Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem 2011, 57:833-840.
• [35]Chen Y, Gelfond JA, McManus LM, Shireman PK: Reproducibility of quantitative RT-PCR array in miRNA expression profiling and comparison with microarray analysis. BMC Genomics 2009, 10:407. BioMed Central Full Text
• [36]Jensen SG, Lamy P, Rasmussen MH, Ostenfeld MS, Dyrskjøt L, Orntoft TF, Andersen CL: Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs. BMC Genomics 2011, 12:435. BioMed Central Full Text
• [37]Sneve M, Figenschau Y, Jorde R: Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects. Eur J Endocrinol 2008, 159:675-684.